Page 1

Radioisotopes in Medicine

U.S. ATOMIC ENERGY COMMISSION/Division of Technical Information


UNITED STATES ATOMIC ENERGY COMMISSION Dr. Glenn T. Seaborg, James T. Ramey Dr. Gerald F. Tape Wilfrid E. Johnson

owe OF A stmis ON

UNDERSTANDING THE ATOM

Chairman

Nuclear energy i s playing a vital role in the life of every man, woman, and child in the United States today. In the y e a r s ahead it will affect increasingly all the peoples of the e a r t h . It is e s s e n t i a l that all Americans gain an understanding of this vital force if they a r e to discharge thoughtfully t h e i r responsibilities a s citizens and if they a r e to r e a l i z e fully the myriad benefits that nuclear energy offers them. The United States Atomic Energy Commission provides this booklet to help you achieve such understanding.

^Edward J. Brunenkant Director Division of Technical Information

This booklet is one of the "Understanding the Atom'' Series. Comments a r e invited on this booklet and others in the s e r i e s ; please send them to the Division of Technical Information, U. S. Atomic Energy Commission, Washington, D. C. 20545. Published as part of the AEC's educational assistance program, the s e r i e s includes these titles: Accelerators Animals in Atomic Research Atomic Fuel Atomic Power Safety Atoms at the Science Fair Atoms in Agriculture Atoms, Nature, ami Man Careers in Atomic Energy Computers Controlled Nuclear Fusion Cryogenics, The Uncommon Cold Direct Conversion of Energy Fallout From Nuclear Tests Food Preservation by Irradiation Genetic Effects of Radiation Microstructure oj Matter Neutron Activation Analysis Nondestructive Testing Nuclear Clocks Nuclear Energy for Desalting Nuclear Power and Merchant Skipping Nuclear Power Plants

Nuclear Propulsion for Space Nuclear Reactors Nuclear Terms, A BrieJ Glossary Our Atomic World Plowshare Plutonium Power from Radioisotopes Power Reactors in Small Packages Radioactive Wastes Radioisotopes and Life Processes Radioisotopes in Industry Radioisotopes in Medicine Rare Earths Research Reactors SNAP, Nuclear Space Reactors Sources ot Nuclear Fuel Synthetic Transuranium Elements The Atom and the Ocean The Chemistry of the Noble Gases Whole Body Counters Your Body and Radiation

A single copy of any one booklet, or of no more than thiec different booklets, may be obtained free by writing to: USAEC, P. 0. BOX 62, OAK RIDGE, TENNESSEE

37830

Complete sets of the s e r i e s a r e available to school and public librarians, and to teachers who can make them available for reference or for use by groups. Requests should be made on school or library letterheads and indicate the proposed u s e . Students and teachers who need other material on specific aspects of nuclear science, or references to other reading material, may also write to the Oak Ridge a d d r e s s . Requests should state the topic of interest exactly, and the u s e intended. In all requests, include " Z i p Code" in return a d d r e s s .

Printed in the United States of America USAEC Division of Technical Information Extension, Oak Ridge, Tennessee August 1967


Radioisotopes in Medicine CONTENTS

PHOTO CREDITS Cover Courtesy Brookhaven National Laboiatory

General ElcLtnc Company Df^cot e) I ol thi L!i»n>iis Mary Elvira Weeks, Journal of Chemical Education Nobel Institute Chicago Wesley Memorial Hospital ( m a m photo) Lawrence Radiation Laboratory (LRL) Brookhaven National Laboratory' LRL LRL Los Alamos Scientific Laboratory LRL Argonne National Laboratory Paul V. Harper, M. D University of Texas. M. D. Ander'iOii Hospital and Tumor Institute

50

1 1 5 5 6 7 9

INTRODUCTION History What Is Radiation ? What Is Radioactivity ? What Are Radioisotopes ? How Are Radioisotopes Used? What Do We Mean by Tracer Atoms?

n 11 14 15 18 18 23 24 25 26 27 28 30 30

DIAGNOSIS Pinpointing Disease Arsenic-74 Chromium-51 Cobalt-60 Iodine-131 Iron-59 Phosphorus-32 Sodium-24 Technetium-99"' Thulium-170 and Gamma Radiography Tritium Activation Analysis Summary

31 31 32 32 33 35 37 38 41

THERAPY A Successful Case General Principles lodine-131 and Iodine-132 Boron-10 Phosphorus-32 Gold-198 Beads, Needles, and Applicators Teletherapy

43

CONCLUSIONS

44

APPENDIX

47

SUGGESTED REFERENCES


^ISitJ-

THE COVER This multi-detector positron scanner is used to locate t u m o r s . A radioisotopelabeled substance is injected into the body and subsequently concentrates in the tumor tissue. The radioisotope emits positrons that immediately decay and produce two gamma rays that travel in opposite directions. These rays a r e detected simultaneously on a pair of opposing detection crystals and a line is established along which the tumor is located. This method is one of many ways doctors use radioisotopes to combat disease. In this, as in many other procedures described in this booklet, the patient remains comfortable at all times.

The following films in the Magic of the Atom Series were produced by the Handel Film Corporation. They a r e each 12V'2 minutes long, have sound, and a r e in black and white. The Atom and the Doctor (1954) shows three applications of radioisotopes in medicine: testing for leukemia and other blood d i s orders with radioiron; diagnosis of thyroid conditions with radioiodine; and cancer r e s e a r c h and therapy with radiogallium. The Atom in the Hospital (1961) (available in color and black and white) illustrates the following facilities at the City of Hope Medical Center in Los Angeles: the stationary cobalt source that is used to treat various forms of malignancies; a rotational therapy unit called the " c e s i u m ring", which revolves around the patient and focuses its beam on the diseased area; and the total-body irradiation chamber for studying the effects of radiation on living things. Research with these facilities is explained. Atomic Biology for Medicine (1956) explains experiments p e r formed to discover effects of radiation on mammals. Atoms for Health (1956) outlines two methods of diagnosis and treatment possible with radiation: a diagnostic test of the liver, and cancer therapy with a radioactive cobalt device. Case histories a r e presented step-by-step. Radiation: Silent Servant of Mankind (1956) depicts four uses of controlled radiation that can benefit mankind: bombardment of plants from a radioactive cobalt source to induce genetic changes for study and crop improvement; irradiation of deep-seated tumors with a beam from a particle accelerator; therapy of thyroid cancer with radioactive iodine; and possibilities for treating brain tumors.

THE AUTHOR Earl W. Phelan is Professor of Chemistry at Tusculum College, Greeneville, Tennessee. From 1952 to 1965, he served as Staff A s s i s tant in the Laboratory Director's Office at Argonne National Laboratory, where his duties included editing the Argonne Reviews and supplying information to students. For 22 years prior to moving to Argonne he served as Head of the Chemistry Department of the Valdosta State College in Georgia. He received his B.S. and P h . D . d e g r e e s from Cornell University.

49


Reports

Radioisotopes in Medicine

Radioisotopes m Medicine (SRlA-13), Stanford Research Institute, Clearinghouse for Federal Scientific and Technical Information, 5285 Port Royal Road, Springfield, Virginia 22151, 1959,180 pp., $3.00.

By E A R L W. P H E L A N

The following r e p o r t s a r e available from the Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402. Isotopes and Radiation Technology (Fall 1963), P. S. Baker, A. F . Rupp, and Associates, Oak Ridge National Laboratory, U. S. Atomic Energy Commission, 123 pp., $0 70. Radioisotopes m Medicine (ORO-125), Gould A. Andrews, Marshall Brucer, and Elizabeth B. Anderson, 1956, 817 pp., $6.00. Applications of Radioisotopes and Radiation m the Life Sciences, Hearings before the Subcommittee on Research, Development, and Radiation of the Joint Committee on Atomic Energy, 87th Congress, 1st Session, 1961, 513 pp., $1 50, Summary Analysis of the Hearings, 23 pp., $0.15.

INTRODUCTION

Motion Pictures

History

Available for loan without charge from the AEC Headquarters Film Library, Division of Public Information, U. S. Atomic Energy Commission, Washington, D. C. 20545 and from other AEC film libraries. Radioisotope Applications in Medicine, 26 minutes, black and white, sound, 1964. Produced by the Educational Broadcasting Corporation under the joint direction of the U. S. Atomic Energy Commission's Divisions of Isotopes Development and Nuclear Education and Training, and the Oak Ridge Institute of Nuclear Studies. This film traces the development of the use of radioisotopes and radiation in the field of medicine from the early work of Hevesy to the present. Descriptions of the following a r e given: study of cholesterol and a r t e r i o s c l e r o s i s , cobalt labeled vitamin Bi2 used to study pernicious anemia, history of iodine radioisotopes and the thyroid, brain tumor localization, determination of body fluid volumes, red cell lifetime, and use of radioisotopes for the treatment of various diseases. Medicine, 20 minutes, sound, color, 1957. Produced by the U. S. Information Agency. Four illustrations of the use of radioactive materials in diagnosis and therapy a r e given exact preoperative location of brain tumor, scanning and charting of thyroids, cancer therapy research, and the study of blood diseases and hardening of the a r t e r i e s . Radiation Protection m Nuclear Medicine, 45 m i n u t e s , sound, color, 1962. Produced by the Fordel Films for the Bureau of Medicine and Surgery of the U. S. Navy. This semitechnical film demonstrates the procedures devised for naval hospitals to protect against the gamma radiation emitted from materials used in radiation therapy.

48

The history of the u s e of radioisotopes for medical purposes i s filled with names of Nobel P r i z e w i n n e r s . It IS inspiring to read how g r e a t minds attacked puzzling phenomena, worked out the theoretical and p r a c t i c a l i m plications of what they observed, and w e r e rewarded by the highest honor in science. For example, in 1895 a G e r man physicist, Wilhelm Konrad Roentgen, n o t i c e d that c e r t a i n c r y s t a l s became luminescent when they were in the vicinity of a highly evacuated e l e c t r i c - d i s charge tube. Objects placed b e tween the tube and the c r y s t a l s s c r e e n e d out some of the invisible radiation that caused this effect, and he observed that the g r e a t e r the d e n s i t y of the object so placed, the g r e a t e r the s c r e e n Wilhelm Roentgen ing effect. He called this new radiation X r a y s , because x was the standard algebraic symbol for an unknown quantity. His discovery won him the first Nobel P r i z e in physics m 1901.

1


A French physicist, Antome Henri Becquerel, newly appointed to the chair of physics at the Ecole Polytechnique in P a n s , saw that this d i s covery opened up a new field for r e s e a r c h and set to work on some of its ramifications. One of the evident features of the production of X rays was the fact that while they were being created, the glass of the vacHenri Becquerel

""™ ^^^ ^^^^ °^ ^ greemsh phosphorescent glow. This suggested to several physicists that substances which become phosphorescent upon exposure to visible light might give off X rays along with the phosphorescence. Becquerel experimented with this by exposing various c r y s t a l s to sunlight and then placing each of them on a black paper envelope enclosing an unexposed photographic plate. If any X r a y s were thus produced, he reasoned, they would penetrate the wrapping and create a developable spot of exposure on the plate. To his delight, he indeed observed just this effect when he used a phosphorescent m a t e r i a l , uranium potassium sulfate. Then he made a confusing d i s covery. For s e v e r a l days there was no sunshine, so he could not expose the phosphorescent m a t e r i a l . For no particular r e a s o n (other than that there was nothing else to do) Becquerel developed a plate that had been in contact with uranium m a t e r i a l in a dark drawer, even though there had been no phosphorescence. The telltale black spot m a r k ing the position of the mineral nevertheless appeared on the developed plate' His conclusion was that uranium in its normal state gave off X r a y s or something s i m i l a r . At this point, P i e r r e Curie, a friend of Becquerel and also a professor of physics in P a n s , suggested to one of his graduate students, his young bride, M a n e , that she study this new phenomenon. She found that both uranium and thorium possessed this property of radioactivity, but also, surprisingly, that some uranium m i n e r a l s were more radioactive than uranium itself. Through a tedious s e r i e s of chemical separations, she obtained from pitchblende (a uranium ore) small amounts of two new elements, polonium

2

I

SUGGESTED REFERENCES Technical Books Radioactive Isotopes m Medicine and Biology, Solomon Silver, Lea & Febiger, Philadelphia, Pennsylvania 19106, 1962, 347 pp., $8.00. Atomic Medicine, Charles F . Behrens and E. Richard King (Eds.), The Williams & Wilkins Company, Baltimore, Maryland 21202, 1964, 766 pp., $18.00. The Practice oj Nuclear Medicine, William H. Blahd, Franz K. Bauer, and Benedict Casben, Charles C Thomas, Publisher, Springfield, lUinois 62703, 1958, 432 pp., $12.50. Piogtess in Atomic Medicine, John H. Lawrence (Ed.), Grune & Stratton, Inc., New York 10016, 1965, volume 1, 240 pp., $9.75. Radiation Biology and Medicine, VJdlter D. Claus (Ed.), AddisonWesley Publishing Company, Reading, Massachusetts 01867, 1958, 944 pp., $17.50. Part 7, Medical Uses of Atomic Radiation, pp. 471-589. Radioisotopes and Radiation, John H. Lawrence, Bernard Manowitz, and Benjamin S. Loeb, McGraw-Hill Book Company, New York 10036, 1964, 131 pp., $18.00. Chapter 1, Medical Diagnosis and Research, pp. 5-45, Chapter 2, Medical Therapy, pp. 49-62.

Popular Books Atoms Today and Tomorrow (revised edition), Margaret O. Hyde, McGraw-Hill Book Company, Inc., New York 10036, 1966, 160 pp., $3.25. Chapter 9, The Doctor and the Atom, pp 79101. Atomic Energy m Medicine, K. E. Hainan, Philosophical Library, Inc., New York 10016, 1958, 157 pp., $6.00. (Out of print but available through libraries.) Teach YourselJ Atomic Physics, James M. Valentine, The Macmillan Company, New York 10011, 1961, 192 pp., $1.95. (Out of print but available through libraries.) Chapter X, Medical and Biological Uses of Radioactive Isotopes, pp, 173-184. Atoms for Peace, Dj.vid O. Woodbury, Dodd, Mead & Company, New York 10016, 1965, 259 pp., $4 50 Pp. 174-191. The Atom at Work, Jacob Sacks, The Ronald P r e s s Company, New York 10010, 1956, 341 pp., $5.50. Chapter 13, Radioactive Isotopes in Hospital and Clinic, pp. 244-264.

Articles Ionizing Radiation and Medicine, S. Warren, Scientific American, 201- 164 (September 1959). Nuclear Nurses Learn to Tame the Atom, W. McGaffin, Today's Health, 37. 62 (December 1959). How Isotopes Aid Medicine in Tracking Down Your Ailments, J. Foster, Today's Health, 42. 40 (May 1964). Nuclear Energy as a Medical Tool, G. W. T r e s s e l , Today's Health, 43: 50 (May 1965).

47


r i e r moves the counter linearly at a slow r a t e . Radiation i s counted and whenever the count reaches the p r e d e t e r mined amount — from one count to many — an electric impulse causes a synchronously moving pen to make a dot on a chart. The scanner, upon reaching the end of a line moves down to the next line and s t a r t s over, eventually producing a complete r e c o r d of the radiation sources it has passed over.

Pierre and Marie

Curie

and radium, and showed that they possessed far g r e a t e r radioactivity than uranium itself. For this work Becquerel and the two Curies were jointly awarded the Nobel P r i z e in physics in 1903. At the outset, Roentgen had noticed that although X r a y s passed through human tissue without causing any immediate sensation, they definitely affected the skin and underlying c e l l s . Soon after exposure, it was evident that X r a y s could cause r e d n e s s of the skin, blistering, and even u l ceration, either in single doses or in repeated s m a l l e r doses. In spite of the h a z a r d s * involved, early experim e n t e r s determined that X r a y s could destroy cancer tissues more rapidly than they affected healthy organs, so a basis was established quite soon for one of Medicine's few methods of curing or at least restraining cancer. The work of the Curies in turn stimulated many studies of the effect of radioactivity. It was not long before exp e r i m e n t e r s learned that naturally radioactive elements — like r a d i u m — w e r e also useful in cancer therapy. These elements emitted gamma r a y s , t which a r e like X r a y s but usually a r e even more penetrating, and their application often could be controlled better than X r a y s . Slowly, over the y e a r s , reliable methods were developed for treatment with these radioactive s o u r c e s , and instruments were d e signed for measuring the quantity of radiation received by the patient. *The early dangers from use of X r a y s , due to incomplete understanding and inadequate shielding, have now been eliminated. t Gamma rays a r e high-energy electromagnetic radiation.

46

3


Geiger-Miiller Counters These have been widely used and a r e versatile in their applications. The potential difference between the electrodes in the Geiger-Miiller tube (similar to an ionization chamber) is high. A single alpha or beta particle ionizes some of the gas within the chamber. In turn these ions strike other gas molecules producing secondary ionization. The r e s u l t is an "avalanche" or high-intensity pulse of e l e c tricity passing between the electrodes. These pulses can be counted electrically and recorded on a meter at r a t e s up to s e v e r a l thousand per minute. Frederic

and Irene

Joliot-Curie

The next momentous advance was made by F r e d e r i c Joliot, a French chemist who m a r r i e d Irene Curie, daughter of P i e r r e and Marie Curie. He discovered in 1934 that when aluminum was bombarded with alpha p a r t i c l e s * from a radioactive source, emission of positrons (positive electrons) was induced. Moreover, the emission continued long after the alpha source was removed. This was the first example of artificially induced radioactivity, and it stimulated a new flood of discoveries. Frederic and Irene JoliotCurie won the Nobel Prize in chemistry in 1935 for this work. Others who followed this discovery with the development of additional ways to create artificial radioactivity w e r e two Americans, H. Richard Crane and C. C. Lauritsen, the British scientists, John Cockcroft and E. T. S. Walton, and an American, Robert J. Van de Graaff. Ernest O. Lawrence, an American physicist, invented the cyclotron (or "atom s m a s h e r " ) , a powerful source of high-energy particles that induced radioactivity in whatever target materials they i m pinged upon. Enrico F e r m i , an Italian physicist, seized upon the idea of using the newly discovered neutron (an electrically neutral particle) and showed that bombardment with neutrons also could induce radioactivity in a target substance. Cockcroft and Walton, Lawrence, and F e r m i all won Nobel P r i z e s for their work. *AIpha particles are large positively charged particles, identical to helium nuclei. For definitions of unfamiliar words see Nuclear Terms. A Brie] Glossary, SL companion booklet in this s e r i e s .

4

Scintillation Counters Since the development of the photoelectric tube and the photomultiplier tube (a combination of photoelectric cell and amplifier), the scintillation counter has become the most popular instrument for most purposes described in this booklet. The flash of light produced when an individual ionizing particle or r a y s t r i k e s a sodium-iodide c r y s t a l i s noted by a photoelectric cell. The intensity of the flash i s a m e a s u r e of the energy of the radiation, so the voltage of the output of the photomultiplier tube is a m e a s u r e of the wavelength of the original gamma ray. The scintillation counter can observe up to a million counts per minute and discriminate sharply between gamma rays of different ene r g i e s . With proper windows it can be used for alpha or beta counts a s well.

Solid State Counters The latest development i s a tiny silicon (transistor-type) diode detector that can be made as small as a grain of sand and placed within the body with very little discomfort.

Scanners Many of the applications described in this booklet r e quire accurate knowledge of the exact location of the radioactive source within the body. Commonly a detecting tube is used having a collimating shield so that it accepts only that radiation that s t r i k e s it head-on. A motor-driven c a r -

45


APPENDIX Measuring Instruments* The measurement of radioactivity must be accomplished indirectly, so use is made of the physical, chemical, and e l e c t r i c a l effects of radiation on m a t e r i a l s . One commonly used effect is that of ionization. Alpha and beta particles ionize gases through which they p a s s , thereby making the g a s e s electrically conductive. A family of counters u s e s this principle- the ionization chamber, the proportional counter, and the Geiger-Miiller counter. Certain c r y s t a l s , sodium iodide being an excellent example, emit flashes of visible light when struck by ionizing radiation. These crystals a r e used in scintillation counters.

Ionization Chambers One of a pair of electrodes is a wire located centrally within a cylinder. The other electrode is the wall of the chamber. Radiation ionizes the gas withm the chamber, permitting the passage of current between the electrodes. The thickness of a window in the chamber wall determines the type of radiation it can m e a s u r e . Only gamma r a y s will pass through a heavy metal wall, glass windows will admit all gammas and most betas, and plastic (Mylar) windows a r e n e c e s s a r y to admit alpha p a r t i c l e s . Counters of this type, when properly calibrated, will m e a s u r e the total amount of radiation received by the body of the w e a r e r .

Proportional Counters This of the energy record rays.

IS a type of ionization chamber in which the intensity electrical pulse it produces is proportional to the of the incoming particle. This makes it possible to alpha particles and discriminate against gamma

*One family of measuring instruments is described in Whole Body Counters, another booklet in this series. These are large devices that make use of scintillating crystals or liquids.

44

Patient application of these new s o u r c e s of bombarding p a r t i c l e s resulted m the creation of small quantities of hundreds of radioactive isotopic s p e c i e s , each with d i s tinctive c h a r a c t e r i s t i c s . In turn, as we shall see, many ways to use radioisotopes have been developed in medical therapy, diagnosis, and r e s e a r c h . By now, more than 3000 hospitals hold licenses from the Atomic Energy Commission to use radioisotopes. In addition, many thousands of doctors, dentists, and hospitals have X - r a y machines that they use for some of the same broad p u r p o s e s . One of the results of all this is that every month new u s e s of radioisotopes a r e developed. More persons are trained every y e a r in methods of radioisotope use and more manufacturers are producing and packaging radioactive m a t e r i a l s . This booklet tells some of the s u c c e s s e s achieved with these m a t e r i a l s for medical purposes.

What Is Radiation? Radiation is the propagation of radiant energy in the form of waves or p a r t i c l e s . It includes electromagnetic radiation ranging from radio waves, infrared heat waves, visible light, ultraviolet light, and X rays to gamma r a y s . It may also include b e a m s of particles of which electrons, positrons, neutrons, protons, deuterons, and alpha p a r t i c l e s are the best known. *

What Is Radioactivity? It took several y e a r s following the basic discovery by Becquerel, and the work of many investigators, to s y s t e m atize the information about this phenomenon. Radioactivity IS defined as the property, possessed by some m a t e r i a l s , of spontaneously emitting alpha or beta p a r t i c l e s or gamma r a y s as the unstable (or radioactive) nuclei of their atoms disintegrate.

*For detailed descriptions of these waves and particles, see Our Atomic World, a companion booklet m this series.


What Are Radioisotopes? In the 19th Century an Englishman, John Dalton, put forth his atomic theory, which stated that all atoms of the same element were exactly alike. This remained unchallenged for 100 y e a r s , until experiments by the British chemist, Frederick Soddy, proved conclusively that the element neon consisted of two different kinds of Frederick Soddy atoms. All were alike in chemical behavior but some had an atomic weight (their m a s s relative to other atoms) of 20 and some a weight of 22. He coined the word isotope to describe one of two or m o r e atoms having the same atomic number but different atomic weights.* Radioisotopes a r e isotopes that a r e unstable, or radioactive, and give off radiation spontaneously. Many r a d i o isotopes a r e produced by bombarding suitable targets with neutrons now readily available inside atomic r e a c t o r s . Some of them, however, a r e more satisfactorily created by the action of protons, deuterons, or other subatomic p a r ticles that have been given high velocities in a cyclotron or similar accelerator. Radioactivity is a p r o c e s s that is practically uninfluenced by any of the factors, such a s temperature and p r e s s u r e , that a r e used to control the rate of chemical reactions. The r a t e of radioactive decay appears to be affected only by the s t r u c t u r e of the unstable (decaying) nucleus. Each radioisotope has its own half-life, which is the time it takes for one half the number of atoms present to decay. These half-lives vary from fractions of a second to millions of y e a r s , depending only upon the atom. We shall s e e that the half-life is one factor considered in choosing a particular isotope for certain u s e s .

*An equivalent statement is that nuclei of isotopes have the s a m e number of protons but different numbers of neutrons.

6

CONCLUSIONS In summary, then, we may say that radioisotopes play an important role in medicine. For the diagnostician, small h a r m l e s s quantities of many isotopes s e r v e a s tools to aid him in gaining information about normal and abnormal life p r o c e s s e s . The usefulness of this information depends upon his ingenuity in devising questions to be answered, apparatus to measure the r e s u l t s , and explanations for the r e s u l t s . For therapeutic u s e s , on the other hand, the important thing to r e m e m b e r i s that radiation damages many kinds of cells, especially while they a r e in the p r o c e s s of division (reproduction)."*^ Cancer cells a r e self-reproducing cells, but do so in an uncontrolled manner. Hence cancer cells are particularly vulnerable to radiation. This treatment r e quires potent sources and correspondingly i n c r e a s e s the hazards of u s e . In all c a s e s , the use of these potentially hazardous m a t e r i a l s belongs under the supervision of the U. S. Atomic Energy Commission.t Licenses a r e issued by the Commission after investigation of the training, ability, and facilities possessed by prospective u s e r s of dangerous quantities. At regular intervals courses a r e given to train individuals in the techniques necessary for safe handling, and graduates of these c o u r s e s are now located in laborat o r i e s all over the country. The future of this field cannot be predicted with certainty. Research in hundreds of laboratories is continuing to add to our knowledge, through new apparatus, new techniques, and new experiments. Necessarily the number of totally new fields is becoming s m a l l e r , but most certainly the number of cases using procedures already established is bound to i n c r e a s e . We foresee steady improvement and growth in all u s e s of radioisotopes in medicine.

*See Your Body and Radiation and The Genetic Effects of Radiation, other booklets in this s e r i e s , for detailed explanations of radiation effects. tThe use of radium is not under AEC control.

43


have to consider that it would be large in volume and consequently difficult to apply. Radiation from such a quantity cannot be focussed; consequently, either much of it will fall upon healthy tissue surrounding the cancer or much of it will be wasted if a narrow passage through the shield is aimed at the tumor. In contrast, a tiny cobalt source p r o vides just as much radiation and more if it can be brought to bear upon the exact spot to be treated. Most interesting of all is the principle by which internal cancers can be treated with a minimum of damage to the skin. Deep x-irradiation has always been the approved treatment for deep-lying c a n c e r s , but until recently this required very cumbersome units. With the modern r o t a tional device shown in the diagram, a very narrow beam is aimed at the patient while the source is mounted upon

HALF-LIFE PATTERN OF STRONTIUM-90

Beginning

1 Half-life

2 Half-lives

3 Half-lives

4 Half-lives

of Life

28 years

56 years

84 years

112 years

Most artificially made radioisotopes have relatively short half-lives. This makes them useful in two ways. F i r s t , it means that very little m a t e r i a l is needed to obtain a significant number of disintegrations. It should be evident that, with any given number of radioactive atoms, the number of disintegrations per second will be inversely proportional to the half-life. Second, by the time 10 halflives have elapsed, the number of disintegrations per s e c ond will have dwindled to V-[02i th^ original number, and the amount of radioactive m a t e r i a l is so small it is usually no longer significant. (Note the decrease in the figure above.)

How Are Radioisotopes Used? a c a r r i e r that revolves completely around him. The patient is positioned carefully so that the lesion to be treated is exactly at the center of the circular path of the c a r r i e r . The result is that the beam s t r i k e s its internal target during the entire circular orbit, but the same amount of radiation is spread out over a belt of skin and tissue all the way around the patient. The damage to any one skin cell is minimized. The advantage of this device over an e a r l i e r device, in which the patient was revolved in a stationary beam, is that the mechanical equipment is much simpler.

42

A radioisotope may be used either as a source of r a d i a tion energy (energy is always released during decay), or as a t r a c e r : an identifying and readily detectable m a r k e r m a t e r i a l . The location of this material during a given treatment can be determined with a suitable instrument even though an unweighably small amount of it is present in a mixture with other m a t e r i a l s . On the following pages we will discuss medical u s e s of individual radioisotopes — first those used as t r a c e r s and then those used for their energy. In general, t r a c e r s a r e used for analysis and

7


diagnosis, and radiant-energy e m i t t e r s a r e used for t r e a t ment (therapy). Radioisotopes offer two advantages. F i r s t , they can be used in extremely small amounts. As little as one-billionth of a gram can be measured with suitable apparatus. Secondly, they can be directed to various definitely known p a r t s of the body. For example, radioactive sodium iodide behaves in the body just the s a m e as normal sodium iodide found in the iodized salt used in many homes. The iodine concentrates in the thyroid gland where it is converted to the hormone thyroxin. Other radioactive, or "tagged", atoms can be routed to bone marrow, red blood cells, the liver, the kidneys, or made to remain in the blood s t r e a m , where they a r e measured using suitable instruments.* Of the three types of radiation, alpha particles (helium nuclei) a r e of such low penetrating power that they cannot be used for measurement from outside the body. Beta particles (electrons) have a moderate penetrating power, therefore they produce useful therapeutic r e s u l t s in the vicinity of their r e l e a s e , and they can be detected by sensitive counting devices. Gamma r a y s a r e highly energetic, and they can be readily detected by counters — radiation measurement d e v i c e s — u s e d outside the body.

Particle or ray Alpha

Paper

Wood

Teletherapy Over 200 teletherapy units a r e now in use in the United States for treatment of patients by using very high intensity s o u r c e s of cobalt-60 (usually) or cesium-137. Units c a r r y ing s o u r c e s with intensities of m o r e than a thousand curies a r e common. Since a curie is the amount of radioactivity in a g r a m of radium that is in equilibrium with its decay products, a 1000-curie s o u r c e is comparable to 2 pounds of pure radium. Neglecting for the moment the scarcity and enormous cost of that much radium (millions of dollars), we

Concrete

I

Beta Gamma

y Relative

penetration

of alpha, beta, and gamma

radiation.

For comparison, a sheet of paper stops alpha p a r t i c l e s , a block of wood stops beta p a r t i c l e s , and a thick concrete wall stops gamma r a y s .

*See Appendix for a description of types of radiation-detection instruments.

8

The cobalt-60 unit at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, employs a 3000-curie source. This unit has a mechanism that alloiisfor rotation therapy about a stationary patient. Many different treatment positions are possible. This patient, shown in position for therapy, has above her chest an auxiliary diaphragm that consists of an expanded metal tray on which blocks of either tungsten or lead are placed to absorb gamma rays and thus shape the field of treatment. In this case they allow for irradiation of the portions of the neck and chest delineated by the lines visible on the patient.

41


difficulty. Radium could be kept in solution, decaying constantly to yield radon. The latter, with a half-life of 4 days, could be sealed into gold seeds 3 by 0.5 m i l l i m e t e r s and left in the patient without much risk, even if he failed to r e t u r n for its removal at exactly the appointed time. The cost was low even if the seeds were lost. During the last 20 y e a r s , other highly radioactive sources have been developed that have been used successfully. Cobalt-60 is one popular m a t e r i a l . Cobalt-59 can be neutron-irradiated in a reactor to yield cobalt-60 with such a high specific activity that a small cylinder of it is m o r e radioactive than the entire world's supply of radium. Cobalt-60 has been encapsulated in gold or silver needles, sometimes of special shapes for adaptation to specific tumors such a s carcinoma of the cervix. Sometimes needles have been spaced at intervals on plastic ribbon that adapts itself readily to the shape of the organ treated. Gold-198 is also an interesting isotope. Since it i s chemically inert in the body, it needs no protective coating, and as is the case with radon, its short half-life makes its u s e simpler in that the time of removal is not of critical importance. Ceramic beads made of yttrium-90 oxide a r e a m o d e r ately new development. One very successful application of this m a t e r i a l has been for the destruction of the pituitary gland. Cancer may be described a s the runaway growth of cells. The secretions of the pituitary gland s e r v e to stimulate cell reproduction, so it was reasoned that destruction of this gland might well slow down growth of a tumor e l s e where in the body. The trouble was that the pituitary is small and located at the base of the brain. Surgical r e moval had brought dramatic relief (not cure) to many patients, but the surgery itself was difficult and hazardous. Tiny yttrium-90 oxide beads, glasslike in nature, can be implanted directly in the gland with much l e s s difficulty and risk, and do the work of destroying the gland with little damage to its surroundings. The key to the s u c c e s s of yttrium-90 is the fact that it is a b e t a - e m i t t e r , and beta r a y s have so little penetrating power that their effect is limited to the immediate a r e a of the implant.

40

In one way or another, the key to the usefulness of r a d i o isotopes lies in the energy of the radiation. When radiation is used for treatment, the energy absorbed by the body is used either to destroy tissue, particularly cancer, or to s u p p r e s s some function of the body. Properly calculated and applied doses of radiation can be used to produce the desired effect with minimum side reactions. Expressed in t e r m s of the usual work or heat units, ergs or calories, the amount of energy associated with a radiation dose is small. The significance lies in the fact that this energy is released in such a way as to produce important changes in the molecular composition of individual cells within the body.

What Do We Mean by Tracer Atoms? When a radioisotope is used as a t r a c e r , the energy of the radiation t r i g g e r s the counting device, and the exact amount of energy from each disintegrating atom is m e a sured. This differentiates the substance being traced from other materials naturally present.

This is the first photoscanner, which was developed in 1954 at the University of Pennsylvania and was retired from service in 1963. When gamma rays emitted by a tracer isotope in the patient's body struck the scanner, a Slashing light produced a dot on photographic film. The intensity of the light varied with the counting rate and thus diseased tissues that differed little from normal tissue except in their uptake of an isotope could be discerned.

9


With one conspicuous exception, it is impossible for a chemist to distinguish any one atom of an element from another. Once ordinary salt gets into the blood s t r e a m , for example, it normally has no characteristic by which anyone can decide what its source was, or which sodium atoms were added to the blood and which were already present. The exception to this is the case in which some of the atoms a r e "tagged" by being made radioactive. Then the radioactive atoms a r e readily identified and their quantity can be measured with a counting device. A radioactive t r a c e r , it is apparent, corresponds in chemical nature and behavior to the thing it t r a c e s . It is a true p a r t of it, and the body t r e a t s the tagged and untagged m a t e r i a l in the s a m e way. A molecule of hemoglobin carrying a radioactive iron atom is still hemoglobin, and the body p r o c e s s e s affect it just as they do an untagged hemoglobin molecule. The difference is that a scientist can use counting devices to follow the t r a c e r molecules wherever they go. It should be evident that t r a c e r s used in diagttosis—to identify disease or improper body function—are p r e s e n t in such small quantities that they a r e relatively h a r m l e s s .

One of the first scans made by a photoscanner. The photorecording (dark bands), superimposed on an X-ray picture Jor orientation, shows radioactivity m a cancer m the patient's neck.

10


r e m a i n suspended or settle out upon the lining. In either case, since they a r e not dissolved, they do not pass through the membranes or cell walls but remain within the cavity. Through its destructive and retarding effect on the cancer cells the radiation inhibits the oozing of fluids. Gold-198 offers s e v e r a l advantages in such c a s e s . It has a short half-life (2.7 days); it is chemically inert and therefore nontoxic; and it emits beta and gamma radiation that is almost entirely absorbed by the tissues in its i m mediate neighborhood. The r e s u l t s have been very encouraging. There is admittedly no evidence of any c u r e s , or even lengthening of life, but there has been marked reduction of discomfort and control of the oozing in over two-thirds of the cases treated.

Their effects a r e analogous to those from the radiation that every one of us continually r e c e i v e s from natural s o u r c e s within and without the body. Therapeutic doses — those given for medical t r e a t m e n t — b y contrast, a r e given to patients with a disease that is in need of control, that is, the physician d e s i r e s to destroy selectively cells or tissues that a r e abnormal. In these c a s e s , therefore, the skill and experience of the attending physician must be applied to limit the effects to the desired benefits, without damage to healthy organs. This booklet i s devoted to these two functions of r a d i o isotopes, diagnosis and therapy; the field of medical r e s e a r c h using radioactive tools is so large that it r e q u i r e s s e p a r a t e coverage.*

Beads, Needles, and Applicators

DIAGNOSIS

Radium salts were the first m a t e r i a l s to be used for radiation treatment of cancer. Being both very expensive and very long-lived, they could not be injected but were used in temporary implants. Radium salts in powder form w e r e packed into tiny hollow needles about 1 centimeter long, which w e r e then sealed tightly to prevent the escape of radon gas. As radium decays (half-life 1620 years) it becomes gaseous radon. The latter is also radioactive, so it must be prevented from escaping. These gold needles could be inserted into tumors and left there until the d e s i r e d dosage had been administered. One difficulty in radium treatment was that the needles were so tiny that on numerous occasions they were lost, having been thrown out with the d r e s s i n g s . Then, both because of their value and their hazard, a frantic search ensued when this happened, not always ending successfully. The fact that radon, the daughter of radium, is constantly produced from its parent, helped to eliminate some of this The needle used for implantation of yttrium-90 pellets into the pituitary gland is shown in the top photograph. In the center X ray the needle is in place and the pellets have just been passed through it into the bone area surrounding the pituitary gland. The bottom X ray shows the needle withdrawn and the pellets within the bone.

38

Pinpointing Disease Mr. P e t e r s , 35-year-old father of four and a resident of Chicago's northwest side, went to a Chicago hospital one winter day after p e r s i s t e n t headaches had made his life m i s e r a b l e . Routine examinations showed nothing a m i s s and his doctor ordered a " b r a i n s c a n " in the hospital's department of nuclear medicine. Thirty minutes before " s c a n time", Mr. P e t e r s was given, by intravenous injection, a minute amount of r a dioactive technetium. This radiochemical had been s t r u c tured so that, if t h e r e w e r e a tumor in his cranium, the radioisotopes would be attracted to it. Then he was positioned so an instrument called a scanner could pass close to his head. As the motor-driven scanner passed back and forth, it picked up the gamma r a y s being emitted by the r a d i o active technetium, much a s a Geiger counter detects other radiation. These r a y s were recorded as black blocks on sensitized film inside the scanner. The r e s u l t was a piece of exposed film that, when developed, bore an architectural likeness or image of Mr. P e t e r ' s cranium. *See Radioisotopes and Life Processes, another booklet in this series, for a discussion of one area of biomedical research.

11


may be a small i n c r e a s e in the number of c a s e s of leukemia among those treated with ^^P compared with the general population. The controversy a r i s e s over whether the ^^P treatment caused the leukemia, or whether it merely p r o longed the lives of the patients until leukemia appeared as it would have in these persons even without treatment. This is probably quibbling, and many doctors believe that the slight unproven r i s k i s worth taking to produce the admitted lengthy freedom from symptoms.

Gold-198

The inset picture shows a brain scan made with a positron scintillation camera. A tumor is indicated by light area above ear. (Light area in facial region is caused by uptake in bone and extracellular space.) The photograph shows a patient, completely comfortable, receiving a brain scan on one of the three rectilinear scanning devices in the nuclear medicine laboratory of a hospital.

The last ailment we shall discuss in this section is the accumulation of large quantities of excess fluid in the chest and abdominal cavities from their linings, as a consequence of the growth of certain types of malignant tumors. Frequent surgical drainage was at one time the only very useful treatment, and of course this was both uncomfortable and dangerous. The use of radioactive colloidal suspensions, p r i m a r i l y colloidal gold-198, has been quite successful in palliative treatment: It does not cure, but it does give marked relief. Radioactive colloids (a colloid is a suspension of one very finely divided substance in some other medium) can be introduced into the abdominal cavity, where they may

Mr. P e t e r s , who admitted to no pain or other adverse reaction from the scanning, was photographed by the scanner from the front and both sides. The procedure took l e s s than an hour. The developed film showed that the technetium had concentrated in one spot, indicating definitely that a tumor was present. Comparison of front and side views made it possible to pinpoint the location exactly. Surgery followed to remove the tumor. Today, thanks to sound and early diagnosis, Mr. P e t e r s is well and back on the job. His case is an example of how radioisotopes a r e used in hospitals and medical centers for diagnosis. In one representative hospital, 17 different kinds of r a dioisotope measurements a r e available to aid physicians in making their diagnoses. All the methods use t r a c e r quantities of m a t e r i a l s . Other hospitals may use only a few of

12

37


Lamps

Thyroid surgery patient 4 days after 5 mc dose of

I

Motor synchronized y with scanner -^

Composite of 10 films

appreciable concentration in the blood-forming tissues (about twice as much inbloodcells a s m general body cells). One other pertinent fact is that these rapidly dividing hematopoietic cells a r e extremely sensitive to radiation. (Hematopoietic cells a r e those that a r e actively forming

Scintillation counters

100 No cases 201 Average age 52 Median survival . . 1 3 2 . Survival for C

>

5 years

91 5°

10 years

70 0°

^ 50 u u ID Q.

Survival of polycythemia vera patients after ^^P therapy.

Oi

i

\

\

0

5

10

15

^ 20

25

Years

blood cells and are therefore those that should be attacked selectively.) The dose required is of course many times that needed for diagnostic studies, and careful observation of the r e s u l t s is necessary to determine that exactly the desired effect has been obtained. There exists some controversy over this course of treatment. No one denies that the lives of patients have been lengthened notably. Nevertheless since the purpose of the procedure is to reduce red cell formation, there exists the hazard of too great a reduction, and the possibility of causing leukemia (a disease of too few red cells). There

36

The first whole body scanner, which was developed at the Donner Laboratory m 1952 and is still being used. The lead collimator contains 10 scintillation counters and moves across the subject. The bed is moved and serial scans are made and then joined together to form a head-to-toe picture of the subject. The diagram shows a scan and the parts of a scanner. (Also see page 21.)

13


them, some may use even m o r e . In any case they a r e merely tools to augment the doctors' skill. Examples of measurements t h a t can be made include blood volume, blood circulation rate, red blood cell turnover, glandular activity, location of cancerous tissue, and r a t e s of formation of bone tissue or blood cells. Of the more than 100 different radioisotopes that have A differential multi-detector debeen used by doctors during veloped at Brookhaven National the past 30 y e a r s , five have Laboratory locates brain tumors received by far the greatest with positron-emitting isotopes. By using many pairs of detection attention. These a r e iodinecrystals, the device shortens the 131, phosphorus-32, gold-198, scanning time and increases acchromium-51, a n d iron-59. curacy. (See cover for another type of positron scanner.) Some others have important u s e s , too, but have been l e s s widely employed than these five. The use of individual r a dioisotopes in making important diagnostic tests makes a fascinating story. Typical instances will be described in the following pages.

Arsenic-74 Brain tumors tend to concentrate certain ions (charged atoms or molecules). When these ions a r e g a m m a - r a y emitters, it is possible to take advantage of the penetrating power of their gamma r a y s to locate the tumor with a scanning device located outside the skull. Arsenic-74 and copper-64 a r e isotopes emitting positrons,* which have one peculiar property. Immediately after a positron is emitted from a nucleus it decays, p r o ducing two gamma r a y s that travel in exactly opposite directions. The scanning device has two detectors called *A positron is an "antielectron' but a positive charge.

W

It has the mass of an electron

actor a few minutes after the boron-10 compound has been injected into a vein. The difficulty is that most boron compounds themselves a r e poisonous to human tissues, and only small concentrations can be tolerated in the blood. Efforts have been made, with some s u c c e s s , to synthesize new boron compounds that have the g r e a t e s t possible degree of selective absorption by the t u m o r s . Both organic and inorganic compounds have been tried, and the degree of selectivity has been shown to be much g r e a t e r for some than for o t h e r s . So far it is too early to say that any c u r e s have been brought about, but r e s u l t s have been very encouraging. The ideal drug, one which will make possible complete destruction of the cancer without harming the patient, is probably still to be devised.

Phosphorus-32 Another disease which is peculiarly open to attack by radioisotopes is polycythemia vera. This is an insidious ailment of a chronic, slowly progressive nature, characterized by an abnormal i n c r e a s e in the number of r e d blood cells, an increase in total blood volume, enlargement of the spleen, and a tendency for bleeding to occur. There is some indication that it may be related to leukemia. Until recent y e a r s there was no very satisfactory t r e a t ment of this malady. The ancient practice of bleeding was as useful as anything, giving temporary relief but not striking at the underlying cause. There is still no true cure, but the use of phosphorus-32 has been very effective in causing disappearance of symptoms for periods from months to y e a r s , lengthening the patient's life considerably. The purpose of the ^^P treatment (using a sodium-radiophosphate solution) is not to destroy the excess of red cells, a s had been tried with some drugs, but r a t h e r to slow down their formation and thereby get at the basic cause. Phosphorus-32 emits pure beta r a y s having an average path in tissue only 2 m i l l i m e t e r s long. Its half-life is 14.3 days. When it is given intravenously it mixes rapidly with the circulating blood and slowly accumulates in tissues that utilize phosphates in their metabolism. This brings 35


scintillation counters, one mounted on each side of the patient's head. The electrical circuitry in the scanner i s such that only those gamma r a y s a r e counted that impinge simultaneously on both counters. This procedure eliminates most of the "noise", or scattered and background radiation.

Chromium-51 Because chromium, in the molecule sodium chromate, attaches itself to red blood cells, it is useful in s e v e r a l kinds of t e s t s . The procedures a r e slightly complicated, but yield useful information. In one, a sample of the patient's blood is withdrawn, stabilized with heparin (to prevent clotting) and incubated with a t r a c e r of radioactive sodium chromate. Excess chromate that is not taken up by the cells is reduced and washed away. Then the radioactivity of the cells is measured, just before injection into the patient. After a suitable time to permit thorough mixing of the added m a t e r i a l throughout the blood s t r e a m , a new blood sample is taken and its radioactivity is measured. The total volume of red blood cells then can be calculated by dividing the total radioactivity of the injected sample by the activity per milliliter of the second sample. In certain types of anemia the patient's red blood cells die before completing the usual r e d - c e l l lifetime of about 120 days. To diagnose this, red cells a r e tagged with chromium-51 (^^Cr) in the manner just described. Then

Spleen scans made with red blood cells, which had been altered by heat treatment and tagged with chromium-51. Such damaged cells are selectively removed by the spleen. A is a normal spleen. B shows an abscess m the spleen. Note dark ring of radioactivity surrounding the lighter area of decreased activity at the central portion of spleen.

15


\

some of them are injected back into the patient and an identical sample is injected into a compatible normal individual. If the t r a c e r shows that the cells' survival time is too short in both recipients to the same degree, the conclusion IS that the r e d cells themselves must be abnormal. On the other hand, if the cell-survival time is normal in the normal individual and too short in the patient, the diagnosis is that the patient's blood contains some substance that d e stroys the red cells. When chromium trichloride, CrCls, is used as the tagging agent, the chromium is bound almost exclusively to plasma proteins, r a t h e r than the red cells. Chromium-51 may thus be used for estimating the volume of plasma c i r c u lating in the heart and blood v e s s e l s . The same type of computation is carried on for red cells (after correction for a small amount of chromium taken up by the red blood cells). This procedure is easy to c a r r y out because the radioactive chromium chloride is injected directly into a vein. An ingenious automatic device has been devised for computing a patient's total blood volume using the ^^Cr measurement of the red blood cell volume as its b a s i s . This determination of total blood volume is of course necessary in deciding whether blood or plasma t r a n s fusions a r e needed in c a s e s involving bleeding, burns, or surgical shock. This ^'Cr procedure was used during the Korean War to determine how much blood had been lost by wounded patients, and helped to save many, many lives. For several y e a r s , iodine-131 has been used as a t r a c e r in determining cardiac output, which is the r a t e of blood flow from the heart It has appeared recently that red blood cells tagged with ^'Cr a r e more satisfactory for this measurement than iodine-labeled albumin in the blood s e r u m It is obvious that the blood-flow r a t e is an extremely important physiological quantity, and a doctor must know it to t r e a t either heart ailments or circulatory d i s turbances. In contrast to the iodine-131 procedure, which r e q u i r e s that an a r t e r y be punctured and blood samples be removed regularly for measurement, chromium labeling merely

16

a half-Me of only 2.33 hours. What this means is that the s a m e weight of radioactive '^^I will give a g r e a t e r radiation dose than '^'l would, and lose its activity rapidly enough to present much l e s s hazard by the time the iodine is r e leased to the blood s t r e a m . Iodine-132 i s therefore often p r e f e r r e d for treatment of this s o r t .

Boron-10 Boron-lO has been used experimentally in the treatment of inoperable brain tumors. Glioblastoma multiforme, a particularly malignant form of cancer, is an invariably fatal disease in which the patient has a probable life expectancy of only 1 y e a r . The tumor extends roots into normal t i s s u e s to such an extent that it is virtually i m possible for the surgeon to remove all malignant tissue even if he removes enough normal brain to affect the functioning of the patient seriously. With or without operation the patient dies within months. This is therefore a case in which any improvement at all i s significantly helpful. The blood-bram b a r r i e r that was mentioned e a r l i e r minimizes the passages of many m a t e r i a l s into normal brain t i s s u e s . But when some organic or inorganic compounds, such as the boron compounds, a r e injected into the blood s t r e a m , they will pass readily into brain tumors and not move into normal brain cells. Boron-10 absorbs slow neutrons readily, and becomes boron-11, which disintegrates almost immediately into alpha p a r t i c l e s and a lithium isotope. Alpha p a r t i c l e s , r e m e m b e r , have very little penetrating power, so all the energy of the alpha radioactivity is expended within the individual tumor cells. This is an ideal situation, for it makes possible destruction of tumor cells with virtually no harm to normal cells, even when the two kinds a r e closely intermingled. Slow neutrons pass through the human body with very little damage, so a fairly strong dose of them can be safely applied to the head. Many of them will be absorbed by the boron-10, and maximum destruction of the cancer will occur, along with minimum hazard to the patient. This treatment is accomplished by placing the head of the patient in a beam of slow neutrons emerging from a nuclear r e -

33


"when the treatment s e r i e s was in p r o g r e s s , the patient's voice was temporarily made worse, but it returned to normal within two months after the treatment ended. The radiation destroyed the cancerous growth, and frequent examinations over 6 y e a r s since have failed to reveal any regrowth. "The treatment spared the patient's vocal cords, and his voice, airway, and food passage w e r e p r e s e r v e d . " This dramatic tale with a happy ending is a good one with which to s t a r t a discussion of how doctors use r a d i o isotopes for treatment of d i s e a s e .

General Principles Radioisotopes have an important role in the treatment of disease, particularly cancer. It is still believed that cancer is not one but s e v e r a l d i s e a s e s with possible multiple causes. Great p r o g r e s s is being made in development of chemicals for relief of cancer. Nevertheless, radiation and surgery a r e still the main methods for treating cancer, and there a r e many conditions in which relief can be obtained through use of radiation. Moreover, the imaginative use of radioisotopes gives much g r e a t e r flexibility in r a d i ation therapy. This is expected to be true for some y e a r s to come even as p r o g r e s s continues. Radioisotopes s e r v e as concentrated s o u r c e s of radiation and frequently a r e localized within the diseased cells or organs. The dose can be computed to yield the maximum therapeutic effect without harming adjacent healthy t i s s u e s . Let us see some of the ways in which this is done.

Iodine-131 and Iodine-132 Iodine, as was mentioned e a r l i e r , concentrates in the thyroid gland, and is converted there to protein-bound iodine that is slowly released to the blood s t r e a m . Iodine131, in concentrations much higher than those used in diagnostic tests, will i r r a d i a t e thyroid cells, thereby damage them, and reduce the activity of an overactive thyroid (hyperthyroidism). The energy is released within the affected gland, and much of it is absorbed t h e r e . Iodine-131 has a half-life of 8.1 days. In contrast, '^^I has

32

In this cardiac output study a probe is positioned over the heart and the passage of iodine-131 labeled human sermn albumin through this area is recorded.

r e q u i r e s that a radiation counter be mounted on the outside of the chest over the aorta (main a r t e r y leaving the heart). A sample of labeled red blood cells is introduced into a vein, and the recording device counts the radioactivity appearing in the aorta as a function of time. Eventually, of course, the counting r a t e (the number of radioactive d i s integrations per second) levels off when the indicator s a m ple has become mixed uniformly in the blood s t r e a m . F r o m the shape of the curve on which the data a r e recorded during the m e a s u r e m e n t s taken before that time, the operator calculates the h e a r t output per second. Obstetricians caring for expectant mothers use red cells tagged with ^'Cr to find the exact location of the placenta. For example, in the condition known as placenta previa, the placenta — the organ within the uterus by which nourishment is transferred from the m o t h e r ' s blood to that of the unborn child — may be placed in such a position that fatal bleeding can occur. A radiation-counting instrument placed over the lower abdomen gives information about the exact location of the placenta. If an abnormal situation exists, the attending physician is then alert and ready to cope with it. The advantages of chromium over iodine-131, which has also been used, a r e that smaller doses a r e required, and that there is no transfer of radioactivity to the fetal circulation.

17


- --"

tp'^rv^'^

Still another common m e a s u r e m e n t using C r - l a b e l e d r e d blood cells is the determination of the amount and location of bleeding from the gastrointestinal tract (the stomach and bowels). The amount is found by simple m e a s u r e m e n t of chromium in the blood that appears in the stools. To find the location is slightly m o r e complicated. The intestinal contents a r e sampled at different levels through an inserted tube, and the radiation of the samples d e t e r mined separately. Finally, gastrointestinal loss of protein can be measured with the aid of ^'Cr-labeled blood s e r u m . The s e r u m is treated with CrClg and then injected into a vein. In s e v e r a l very serious ailments there is serious loss of blood p r o tein through the intestines. In these conditions the ^'Cr level in the intestinal excretions is high, and this a l e r t s the doctor to apply remedial m e a s u r e s .

Cobalt-60 Vitamin B12 is a cobalt compound. Normally the few milligrams of B12 in the body a r e stored in the liver and released to the blood s t r e a m as needed. In pernicious anemia, a potentially fatal but curable disease, the B12 content of the blood falls from the usual level of 3 0 0 - 9 0 0 m i c r o m i c r o g r a m s per milliliter (ml) to 0 to 100 m i c r o m i c r o g r a m s per ml. The administration of massive doses of B12 i s the only known remedy for this condition. If the B12 is labeled with radioactive cobalt, its passage into the blood s t r e a m may be observed by several different methods. The simplest is to give the B12 by mouth, and after about 8 hours study the level of cobalt radioactivity in the blood. Cobalt-60 has been used for s e v e r a l y e a r s , but recently cobalt-58 has been found more satisfactory. It has a half-life of 72 days while ^"Co has a 5.3-year halflife. This reduces greatly the amount of radiation to the patient's liver by the retained radioactivity.

''i^t

fT),

nostic skill. All radioisotope p r o c e d u r e s a r e m e r e l y tools to aid the skilled physician. As the practice of medicine has changed from an a r t to a science, radioisotopes have played a useful part.

THERAPY A Successful Case A doctor recently told this story about a cancer patient who was cured by irradiation with cobalt-60. " A 75-year-old white male patient, who had been hoarse for one month, was treated unsuccessfully with the usual medications given for a bad cold. Finally, examination of his larynx revealed an ulcerated swelling on the right vocal cord. A biopsy (microscopic examination of a tissue sample) was made, and it was found the swelling was a squamous-cell cancer. "Daily radiation treatment using a cobalt-60 device was started and continued for 31 days. This was in September 1959. The cobalt-60 unit is one that can be operated by remote control. It positions radioactive cobalt over a collimator, which determines the size of the radiation beam reaching the patient. The machine may be made to rotate around the patient or can be used at any desired angle or position.

Iodine-131 Like chromium-51, iodine is a versatile t r a c e r element. It is used to determine blood volume, cardiac output, plasma volume, liver activity, fat metabolism, thyroid

18

31


Activation Analysis Another booklet in this series, Neutron Activation A7ialysis, discusses a new p r o c e s s by which microscopic quantities of many different materials may be analyzed accurately. Neutron irradiation of these samples changes some of their atoms to radioactive isotopes. A multichannel analyzer instrument gives a record of the concentration of any of about 50 of the known elements. One use of this technique involved the analysis of a hair from Napoleon's head. More than 100 y e a r s after his death it was shown that the French Emperor had been given arsenic in large quantities and that this possibly caused his death. The ways in which activation analysis can be applied to medical diagnosis a r e at present largely limited to toxicology, the study of poisons, but the future may bring new possibilities. Knowledge is still being sought, for example, about the physiological role played by minute quantities of some of the elements found in the body. The ability to determine accurately a few parts per million of "trace e l e m e n t s " in the various tissues and body fluids is expected to provide much useful i n f o r m a t i o n as to the functions of these materials.

Summary A large number of different radioisotopes have been used for measurement of disease conditions in the human body. They may m e a s u r e liquid volumes, r a t e s of flow or r a t e s of transfer through organs or membranes; they may show the behavior of internal organs; they may differentiate between normal and malignant t i s s u e s . Hundreds of hospitals a r e now making thousands of these tests annually. This does not mean that all the diagnostic problems have been solved. Much of the work is on an experimental rather than a routine b a s i s . Improvements in techniques a r e still being made. As quantities of radioisotopes available for these purposes grow, and as the cost continues to drop, it is expected there will be still more applications. Finally, this does not mean we no longer need the doctor's diag-

30

(^

ÂŽ

ÂŽ

A linear photoscanner produced these pictures of (A) a normal thyroid, (B) an enlarged thyroid, and (C) a cancerous thyroid.

cancer m e t a s t a s e s , brain tumors, and the size, shape, and activity of the thyroid gland. Because of its unique connection with the thyroid gland, iodine-131 is most valuable in m e a s u r e m e n t s connected with that organ. Thyroxin, an iodine compound, is manufactured in the thyroid gland, and t r a n s f e r r e d by the blood s t r e a m to the body t i s s u e s . The thyroxin helps to govern the oxygen consumption of the body and therefore helps control its metabolism. Proper production of thyroxin is essential to the proper utilization of nutrients. Lowered metabolism means increased body weight. Lowered thyroid activity may mean expansion of the gland, causing one form of goiter. Iodine-131 behaves in the body just as the natural nonradioactive isotope, iodine-127, does, but the radioactivity p e r m i t s observation from outside the body with some form of radiation counter. Iodine can exist in the body in many different chemical compounds, and the counter can tell where it is but not in what form. Hence chemical manipulation is n e c e s s a r y in applying this technique to different diagnostic p r o c e d u r e s . The thyroid gland, which is located at the base of the neck, is very efficient in trapping inorganic iodide from the blood s t r e a m , concentrating and storing the iodinecontaining m a t e r i a l and gradually releasing it to the blood s t r e a m in the form of protein-bound iodine (PBI). One of the common diagnostic procedures for d e t e r m i n ing thyroid function, therefore, is to m e a s u r e the p e r c e n t age of an administered dose of '^h that is taken up by the gland. Usually the patient is given a very small dose of radioactive sodium iodide solution to drink, and two hours later the amount of iodine in the gland is determined by measuring the radiation coming from the neck a r e a . In

19


Screening Test for Hyperthyroidism

S 60%

Hyperactive

oa^°g°

^ o 20%

0%

Normal

46% Uptake in 24 hours (Percent of administered dosej

hyperthyroidism, or high thyroid gland activity, the gland removes iodide ions from the blood s t r e a m m o r e rapidly than normal. This simple procedure has been used widely. One difficulty in using it is that its s u c c e s s i s dependent upon the time interval between injection and measurement. An overactive gland both concentrates iodine rapidly and also

It is especially itnportant in isotope studies on infants and small children that the radiation exposure be low. By carrying out studies in the whole body counter room, the administered dose can be greatly reduced. The photographs illustrate a technique of measuring radioiodine uptake m the thyroid gland with extremely small amounts of a mixture oJ iodine-131 and iodine-125. A shows a small television set that is mounted above the crystal in such a way that good viewing requires that the head be kept in the desired position. This helps solve the problem of keeping small children still during a 15-minute counting period. B shows a child m position for a thyroid uptake study.

20

100%

determination of total body water. A small sample of heavy water was given either intravenously or orally, and time was allowed for it to mix uniformly with all the water in the body (about 4 to 6 hours). A sample was then obtained of the mixed water and analyzed for its heavy water content. This procedure was useful but it was hard to make an accurate analysis of low concentrations of heavy water. More recently, however, tritium (^H) (radioactive hydrogen) has been produced in abundance. Its oxide, tritiated water (^H20), is chemically almost the same as ordinary water, but physically it may be distinguished by the beta r a y s given off by the tritium. This very soft (low-energy) beta ray r e q u i r e s the use of special counting equipment, either a windowless flow-gas counter or a liquid scintillator, but with the proper techniques accurate m e a s u r e m e n t is possible. The total body water can then be computed by the general isotope dilution formula used for measuring blood plasma volume.

The total body water is determined by the dilution method using tritiated water. This technician is purifying a urine sample so that the tritium content can be determined and the total body 'water calculated.

29


isF

A leclinician holds an inexpensive X-ray unit that was developed Argonne National Laboratory. its size with the standard X-ray shown at left and above.

portable by the Compare machine

Still more recently, '^^I has been used very successfully in a portable device as a low-energy gamma source for radiography. The gamma r a y s from this source are sufficiently penetrating for photographing the a r m s and legs, and the necessary shielding is easily supplied to protect the operator. By contrast with l a r g e r devices, the gammaray source can be as small as one-tenth millimeter in diameter, virtually a point source; this makes possible maximum sharpness of image. The latest device, using up to one curie* of ^^^I, weighs 2 pounds, yet has adequate shielding for the operator. It is truly portable. If this X-ray source is combined with a rapid developing photographic film, a physician can be completely freed from dependence upon the hospital laboratory for emergency X r a y s . A finished print can be ready for inspection in 10 seconds. The doctor thus can decide quickly whether it is safe to move an accident victim, for instance. In military operations, similarly, it becomes a simple matter to examine wounded soldiers in the field where conventional equipment is not available.

Tritium More than 30 years ago, when deuterium (heavy hydrogen) was first discovered, heavy water (D2O) was used for the *The curie is the basic unit of radiation Intensity. One curie is approximately the amount of radioactivity in 1 gi-am of radium.

28

discharges it back to the blood s t r e a m as PBI more rapidly than n o r m a l . Modifications of the test have been made to compare the amount of iodine-131 that was administered with the amount circulating in the blood as PBI. The system r e q u i r e s chemical separation of the two forms of iodine from a sample of blood removed from a vein, followed by s e p a r a t e counting. This computation of the "conversion r a t i o " of radioactive plasma PBI to p l a s m a total '^'l gives r e s u l t s that a r e l e s s subject to m i s i n terpretation. To determine local activity in s m a l l portions of the thyroid, an automatic scanner is used. A collimator* shields the detector (a Geiger-Miiller tube or scintillating crystal) so that only those impulses originating within a very small a r e a a r e accepted by the instrument. The d e tector is then moved back and forth slowly over the entire a r e a and the radiation is automatically recorded at definite intervals, creating a " m a p " of the active a r e a . In c a s e s where lumps, or nodules, have been discovered in the thyroid, the map is quite helpful in distinguishing between cancerous and benign nodules. The former a r e almost always l e s s radioactive than surrounding t i s s u e s . Fragments of cancerous thyroid tissue may migrate to other p a r t s of the body and grow there. These new cancers a r e known as metastatic c a n c e r s and a r e a signal of an advanced state of d i s e a s e . In such a situation even complete surgical removal of the original cancer may not save the Seven serial scans made with the whole body scanner were put together to provide a whole body scan of this patient with thyroid cancer that had spread to the lung. One millic urie of iodine-131 was administered and the scan made 72 hours later. Note the uptake in the lung. This patient was successfully treated with large doses of iodine-131. *A collimator is a focusing device consisting of a s e r i e s of slits between blocks of shielding material. Consult the Appendix for descriptions of other instruments mentioned h e r e .

21


patient. If these m e t a s t a s e s a r e capable of concentrating iodine (less than 10% of them are), they can be located by scanning the whole body in the manner that was just described. When a thyroid cancer is discovered, therefore, a doctor may look for m e t a s t a s e s before deciding to operate. Human blood s e r u m albumin labeled with '^'l is used for measurement of the volume of circulating plasma. The procedure is quite similar to that used with radioactive chromium. lodinated human s e r u m albumin labeled with '^'l is injected into a vein. Then, after allowing time for complete mixing of the sample with the blood, a second sample i s counted using a scintillation counter.

Âť

Time-lapse motion pictures of the liver of a 3-year-old girl were made with the scintillation camera 1 hour after injection of 50 microcuries of iodine-131-labeled rose bengal dye. This child was born without a bile-duct system and an artificial bile duct had been created surgically. She developed symptoms that caused concern that the duct had closed. These scans show the mass of material containing the radioactive material (small light area) moving downward and to the right, indicating that the duct was still open. For many y e a r s , a dye known as rose bengal has been used in testing liver function. About 10 years ago this procedure was improved by labeling the dye with ^^^I. When this dye is injected into a vein it goes to the liver, which removes it from the blood s t r e a m and transfers it to the intestines to be excreted. The rate of disappearance of the dye from the blood s t r e a m is therefore a m e a s u r e of the liver activity. Immediately after administration of the radioactive dye, counts a r e recorded, preferably continuously from s e v e r a l s i t e s with shielded, collimated d e t e c t o r s . One counter is placed over the side of the head or the thigh to r e c o r d the clearance of the dye from the blood s t r e a m . A second is placed over the liver, and a third over the abdomen to record the passage of the dye into the small intestine. Human s e r u m albumin labeled with '"'^I is sometimes used for location of brain t u m o r s . It appears that tumors

22

Using a "nuclear cow" to get technetium from its parent isotope. The "cow" is being fed saltwater through a tube. The saltwater drains through a high-radiation (hot) isotope. The resultant drip-off is a daughter such as technetium99"'. This new, mild isotope can be mixed with other elements and these become the day's supply of radioisotopes for other scans. Technetium99*" decays in 6 hours. Thus greater amounts, with less possibility of injury, can be administered and a better picture results.

Thulium-170 and Gamma Radiography

'

For y e a r s it has been recognized that there would be many uses for a truly portable device for taking X-ray pictures — one that could be carried by the doctor to the bedside or to the scene of an accident. Conventional X-ray equipment has been in use by doctors for many y e a r s , and highly efficient apparatus has become indispensable, e s pecially in treating bone conditions. There i s , however, a need for a means of examining patients who cannot be moved to a hospital X-ray room, and are located where e l e c t r i c current s o u r c e s a r e not available. A few y e a r s ago, a unit was devised that weighed only a few pounds, and could take "X-ray p i c t u r e s " (actually gamma radiographs) using the gamma r a y s from the radioisotope thulium-170. The thulium source is kept inside a lead shield, but a photographic s h u t t e r - r e l e a s e cable can be p r e s s e d to move it momentarily over an open port in the shielding. The picture is taken with an exposure of a few seconds. A somewhat similar device u s e s strontium-90 as the source of beta radiation that in turn stimulates the emission of gamma r a y s from a target within the instrument.

27


route of ^''Na

Technetium-99"^ Because of its short half-life of six hours, technetium99™* is coming into use for diagnosis using scanning d e vices, particularly for brain t u m o r s . It l a s t s such a short time it obviously cannot be kept in stock, so it is prepared by the beta decay of molybdenum-99.t A stock of molybdenum is kept in a shielded container in which it undergoes radioactive decay yielding technetium. Every morning, as the technetium is needed, it is extracted from its parent by a brine solution. This general procedure of extracting a short-lived isotope from its parent is also used in other c a s e s . We shall see later that radon gas is obtained by an analogous method from its parent, radium. *The superscript m after this isotope indicates an excited state of the atom. tAs radioactive nuclei disintegrate, they change to other radioactive forms — their " d a u g h t e r " products. Every radioisotope is thus part of a chain or s e r i e s of steps that ends with a stable form. Technetium-99'" is a daughter product of molybdenum-99; it decays by a process known as isomeric transition to a state of lower energy and longer half-life.

26

alter a normal " b a r r i e r " between the brain and blood in such a manner that the labeled albumin can penetrate tumorous tissues although it would be excluded from healthy brain tissue. The brain behaves almost uniquely among body tissues in that a "blood-brain b a r r i e r " exists, so that substances injected into the blood s t r e a m will not pass into brain cells although they will p a s s readily into muscular tissue. This blood-brain b a r r i e r does not exist in brain t u m o r s . A systematic scanning of the skull then permits location of these cancerous "hot spots".

Iron-59 Iron is a n e c e s s a r y constituent of r e d blood cells, so its radioactive form, ^^Fe, has been used frequently in m e a surement of the r a t e of formation of r e d cells, the lifetime of r e d cells, and r e d cell volumes. The labeling is m o r e difficult than labeling with chromium for the s a m e purposes, so this procedure no longer has the importance it once had. On the other hand, direct m e a s u r e m e n t of absorption of iron by the digestive t r a c t can be accomplished only by using ^^Fe. In achlorhydria the g a s t r i c juice in the stomach i s deficient in hydrochloric acid, and this condition has been shown to lower the iron absorption. A normal diet contains much m o r e iron than the body needs, but in special

23


little penetrating power. This fact limits the use of the test to skin c a n c e r s or to cancers exposed by surgery. Some kinds of brain tumors, for instance, a r e difficult to distinguish visually from the healthy brain tissue. In such c a s e s , the patient may be given ^^P labeled phosphate intravenously some hours before surgery. A tiny betasensitive probe counter then can be moved about within the operative site to indicate to the surgeon the limits of the cancerous a r e a .

Sodium-24

This multiple-port scintillation counter is used for iron-kmetic studies. The tracer dose of iron-59 is administered into the arm vein and then the activities in the bone marrow, liver, and spleen are recorded simultaneously with counters positioned over these areas, and show distribution of iron-59 as a function of time. When the data are analyzed m conjunction with iron-59 content m blood, information can be obtained about sites of red blood cell production and destruction.

cases, sometimes called "tired blood" in advertising for medicines, iron compounds a r e prescribed for the patient. If ^^Fe is included, its appearance in the blood s t r e a m can be monitored and the effectiveness of the medication noted.

Phosphorus-32 The phosphate ion is a normal constituent of the blood. In many kinds of tumors, phosphates seem to be present in the cancerous tissue in a concentration s e v e r a l times that of the surrounding healthy tissue. This offers a way of using phosphorus-32 to distinguish between cancer cells and their neighbors. Due to the fact that ^^P gives off beta r a y s but no gammas, the counter must be placed very close to the suspected tissue, since beta particles have very

24

Normal blood is about 1% sodium chloride or ordinary salt. This fact makes possible the use of ^*Na in some measurements of the blood and other fluids. The figure illustrates this technique. A sample of ^^NaCl solution is injected into a vein in an a r m or leg. The time the radioisotope a r r i v e s at another p a r t of the body is detected with a shielded radiation counter. The elapsed time is a good indication of the presence or absence of constrictions or obstructions in the circulatory system.

© -^*NaCI solution injected

© Blood carries ^''NaCI to both legs

Site of constriction

©

High r e a d i n g good circulation

© Low readingpoor circulation

The passage of blood through the heart may also be measured with the aid of sodium-24. Since this isotope emits gamma r a y s , measurement is done using counters on the outside of the body, placed at appropriate locations above the different sections of the heart.

25


little penetrating power. This fact limits the use of the test to skin c a n c e r s or to cancers exposed by surgery. Some kinds of brain tumors, for instance, a r e difficult to distinguish visually from the healthy brain tissue. In such c a s e s , the patient may be given ^^P labeled phosphate intravenously some hours before surgery. A tiny betasensitive probe counter then can be moved about within the operative site to indicate to the surgeon the limits of the cancerous a r e a .

Sodium-24

This multiple-port scintillation counter is used for iron-kmetic studies. The tracer dose of iron-59 is administered into the arm vein and then the activities in the bone marrow, liver, and spleen are recorded simultaneously with counters positioned over these areas, and show distribution of iron-59 as a function of time. When the data are analyzed m conjunction with iron-59 content m blood, information can be obtained about sites of red blood cell production and destruction.

cases, sometimes called "tired blood" in advertising for medicines, iron compounds a r e prescribed for the patient. If ^^Fe is included, its appearance in the blood s t r e a m can be monitored and the effectiveness of the medication noted.

Phosphorus-32 The phosphate ion is a normal constituent of the blood. In many kinds of tumors, phosphates seem to be present in the cancerous tissue in a concentration s e v e r a l times that of the surrounding healthy tissue. This offers a way of using phosphorus-32 to distinguish between cancer cells and their neighbors. Due to the fact that ^^P gives off beta r a y s but no gammas, the counter must be placed very close to the suspected tissue, since beta particles have very

24

Normal blood is about 1% sodium chloride or ordinary salt. This fact makes possible the use of ^*Na in some measurements of the blood and other fluids. The figure illustrates this technique. A sample of ^^NaCl solution is injected into a vein in an a r m or leg. The time the radioisotope a r r i v e s at another p a r t of the body is detected with a shielded radiation counter. The elapsed time is a good indication of the presence or absence of constrictions or obstructions in the circulatory system.

© -^*NaCI solution injected

© Blood carries ^''NaCI to both legs

Site of constriction

©

High r e a d i n g good circulation

© Low readingpoor circulation

The passage of blood through the heart may also be measured with the aid of sodium-24. Since this isotope emits gamma r a y s , measurement is done using counters on the outside of the body, placed at appropriate locations above the different sections of the heart.

25


route of ^''Na

Technetium-99"^ Because of its short half-life of six hours, technetium99™* is coming into use for diagnosis using scanning d e vices, particularly for brain t u m o r s . It l a s t s such a short time it obviously cannot be kept in stock, so it is prepared by the beta decay of molybdenum-99.t A stock of molybdenum is kept in a shielded container in which it undergoes radioactive decay yielding technetium. Every morning, as the technetium is needed, it is extracted from its parent by a brine solution. This general procedure of extracting a short-lived isotope from its parent is also used in other c a s e s . We shall see later that radon gas is obtained by an analogous method from its parent, radium. *The superscript m after this isotope indicates an excited state of the atom. tAs radioactive nuclei disintegrate, they change to other radioactive forms — their " d a u g h t e r " products. Every radioisotope is thus part of a chain or s e r i e s of steps that ends with a stable form. Technetium-99'" is a daughter product of molybdenum-99; it decays by a process known as isomeric transition to a state of lower energy and longer half-life.

26

alter a normal " b a r r i e r " between the brain and blood in such a manner that the labeled albumin can penetrate tumorous tissues although it would be excluded from healthy brain tissue. The brain behaves almost uniquely among body tissues in that a "blood-brain b a r r i e r " exists, so that substances injected into the blood s t r e a m will not pass into brain cells although they will p a s s readily into muscular tissue. This blood-brain b a r r i e r does not exist in brain t u m o r s . A systematic scanning of the skull then permits location of these cancerous "hot spots".

Iron-59 Iron is a n e c e s s a r y constituent of r e d blood cells, so its radioactive form, ^^Fe, has been used frequently in m e a surement of the r a t e of formation of r e d cells, the lifetime of r e d cells, and r e d cell volumes. The labeling is m o r e difficult than labeling with chromium for the s a m e purposes, so this procedure no longer has the importance it once had. On the other hand, direct m e a s u r e m e n t of absorption of iron by the digestive t r a c t can be accomplished only by using ^^Fe. In achlorhydria the g a s t r i c juice in the stomach i s deficient in hydrochloric acid, and this condition has been shown to lower the iron absorption. A normal diet contains much m o r e iron than the body needs, but in special

23


patient. If these m e t a s t a s e s a r e capable of concentrating iodine (less than 10% of them are), they can be located by scanning the whole body in the manner that was just described. When a thyroid cancer is discovered, therefore, a doctor may look for m e t a s t a s e s before deciding to operate. Human blood s e r u m albumin labeled with '^'l is used for measurement of the volume of circulating plasma. The procedure is quite similar to that used with radioactive chromium. lodinated human s e r u m albumin labeled with '^'l is injected into a vein. Then, after allowing time for complete mixing of the sample with the blood, a second sample i s counted using a scintillation counter.

Âť

Time-lapse motion pictures of the liver of a 3-year-old girl were made with the scintillation camera 1 hour after injection of 50 microcuries of iodine-131-labeled rose bengal dye. This child was born without a bile-duct system and an artificial bile duct had been created surgically. She developed symptoms that caused concern that the duct had closed. These scans show the mass of material containing the radioactive material (small light area) moving downward and to the right, indicating that the duct was still open. For many y e a r s , a dye known as rose bengal has been used in testing liver function. About 10 years ago this procedure was improved by labeling the dye with ^^^I. When this dye is injected into a vein it goes to the liver, which removes it from the blood s t r e a m and transfers it to the intestines to be excreted. The rate of disappearance of the dye from the blood s t r e a m is therefore a m e a s u r e of the liver activity. Immediately after administration of the radioactive dye, counts a r e recorded, preferably continuously from s e v e r a l s i t e s with shielded, collimated d e t e c t o r s . One counter is placed over the side of the head or the thigh to r e c o r d the clearance of the dye from the blood s t r e a m . A second is placed over the liver, and a third over the abdomen to record the passage of the dye into the small intestine. Human s e r u m albumin labeled with '"'^I is sometimes used for location of brain t u m o r s . It appears that tumors

22

Using a "nuclear cow" to get technetium from its parent isotope. The "cow" is being fed saltwater through a tube. The saltwater drains through a high-radiation (hot) isotope. The resultant drip-off is a daughter such as technetium99"'. This new, mild isotope can be mixed with other elements and these become the day's supply of radioisotopes for other scans. Technetium99*" decays in 6 hours. Thus greater amounts, with less possibility of injury, can be administered and a better picture results.

Thulium-170 and Gamma Radiography

'

For y e a r s it has been recognized that there would be many uses for a truly portable device for taking X-ray pictures — one that could be carried by the doctor to the bedside or to the scene of an accident. Conventional X-ray equipment has been in use by doctors for many y e a r s , and highly efficient apparatus has become indispensable, e s pecially in treating bone conditions. There i s , however, a need for a means of examining patients who cannot be moved to a hospital X-ray room, and are located where e l e c t r i c current s o u r c e s a r e not available. A few y e a r s ago, a unit was devised that weighed only a few pounds, and could take "X-ray p i c t u r e s " (actually gamma radiographs) using the gamma r a y s from the radioisotope thulium-170. The thulium source is kept inside a lead shield, but a photographic s h u t t e r - r e l e a s e cable can be p r e s s e d to move it momentarily over an open port in the shielding. The picture is taken with an exposure of a few seconds. A somewhat similar device u s e s strontium-90 as the source of beta radiation that in turn stimulates the emission of gamma r a y s from a target within the instrument.

27


isF

A leclinician holds an inexpensive X-ray unit that was developed Argonne National Laboratory. its size with the standard X-ray shown at left and above.

portable by the Compare machine

Still more recently, '^^I has been used very successfully in a portable device as a low-energy gamma source for radiography. The gamma r a y s from this source are sufficiently penetrating for photographing the a r m s and legs, and the necessary shielding is easily supplied to protect the operator. By contrast with l a r g e r devices, the gammaray source can be as small as one-tenth millimeter in diameter, virtually a point source; this makes possible maximum sharpness of image. The latest device, using up to one curie* of ^^^I, weighs 2 pounds, yet has adequate shielding for the operator. It is truly portable. If this X-ray source is combined with a rapid developing photographic film, a physician can be completely freed from dependence upon the hospital laboratory for emergency X r a y s . A finished print can be ready for inspection in 10 seconds. The doctor thus can decide quickly whether it is safe to move an accident victim, for instance. In military operations, similarly, it becomes a simple matter to examine wounded soldiers in the field where conventional equipment is not available.

Tritium More than 30 years ago, when deuterium (heavy hydrogen) was first discovered, heavy water (D2O) was used for the *The curie is the basic unit of radiation Intensity. One curie is approximately the amount of radioactivity in 1 gi-am of radium.

28

discharges it back to the blood s t r e a m as PBI more rapidly than n o r m a l . Modifications of the test have been made to compare the amount of iodine-131 that was administered with the amount circulating in the blood as PBI. The system r e q u i r e s chemical separation of the two forms of iodine from a sample of blood removed from a vein, followed by s e p a r a t e counting. This computation of the "conversion r a t i o " of radioactive plasma PBI to p l a s m a total '^'l gives r e s u l t s that a r e l e s s subject to m i s i n terpretation. To determine local activity in s m a l l portions of the thyroid, an automatic scanner is used. A collimator* shields the detector (a Geiger-Miiller tube or scintillating crystal) so that only those impulses originating within a very small a r e a a r e accepted by the instrument. The d e tector is then moved back and forth slowly over the entire a r e a and the radiation is automatically recorded at definite intervals, creating a " m a p " of the active a r e a . In c a s e s where lumps, or nodules, have been discovered in the thyroid, the map is quite helpful in distinguishing between cancerous and benign nodules. The former a r e almost always l e s s radioactive than surrounding t i s s u e s . Fragments of cancerous thyroid tissue may migrate to other p a r t s of the body and grow there. These new cancers a r e known as metastatic c a n c e r s and a r e a signal of an advanced state of d i s e a s e . In such a situation even complete surgical removal of the original cancer may not save the Seven serial scans made with the whole body scanner were put together to provide a whole body scan of this patient with thyroid cancer that had spread to the lung. One millic urie of iodine-131 was administered and the scan made 72 hours later. Note the uptake in the lung. This patient was successfully treated with large doses of iodine-131. *A collimator is a focusing device consisting of a s e r i e s of slits between blocks of shielding material. Consult the Appendix for descriptions of other instruments mentioned h e r e .

21


Screening Test for Hyperthyroidism

S 60%

Hyperactive

oa^°g°

^ o 20%

0%

Normal

46% Uptake in 24 hours (Percent of administered dosej

hyperthyroidism, or high thyroid gland activity, the gland removes iodide ions from the blood s t r e a m m o r e rapidly than normal. This simple procedure has been used widely. One difficulty in using it is that its s u c c e s s i s dependent upon the time interval between injection and measurement. An overactive gland both concentrates iodine rapidly and also

It is especially itnportant in isotope studies on infants and small children that the radiation exposure be low. By carrying out studies in the whole body counter room, the administered dose can be greatly reduced. The photographs illustrate a technique of measuring radioiodine uptake m the thyroid gland with extremely small amounts of a mixture oJ iodine-131 and iodine-125. A shows a small television set that is mounted above the crystal in such a way that good viewing requires that the head be kept in the desired position. This helps solve the problem of keeping small children still during a 15-minute counting period. B shows a child m position for a thyroid uptake study.

20

100%

determination of total body water. A small sample of heavy water was given either intravenously or orally, and time was allowed for it to mix uniformly with all the water in the body (about 4 to 6 hours). A sample was then obtained of the mixed water and analyzed for its heavy water content. This procedure was useful but it was hard to make an accurate analysis of low concentrations of heavy water. More recently, however, tritium (^H) (radioactive hydrogen) has been produced in abundance. Its oxide, tritiated water (^H20), is chemically almost the same as ordinary water, but physically it may be distinguished by the beta r a y s given off by the tritium. This very soft (low-energy) beta ray r e q u i r e s the use of special counting equipment, either a windowless flow-gas counter or a liquid scintillator, but with the proper techniques accurate m e a s u r e m e n t is possible. The total body water can then be computed by the general isotope dilution formula used for measuring blood plasma volume.

The total body water is determined by the dilution method using tritiated water. This technician is purifying a urine sample so that the tritium content can be determined and the total body 'water calculated.

29


Activation Analysis Another booklet in this series, Neutron Activation A7ialysis, discusses a new p r o c e s s by which microscopic quantities of many different materials may be analyzed accurately. Neutron irradiation of these samples changes some of their atoms to radioactive isotopes. A multichannel analyzer instrument gives a record of the concentration of any of about 50 of the known elements. One use of this technique involved the analysis of a hair from Napoleon's head. More than 100 y e a r s after his death it was shown that the French Emperor had been given arsenic in large quantities and that this possibly caused his death. The ways in which activation analysis can be applied to medical diagnosis a r e at present largely limited to toxicology, the study of poisons, but the future may bring new possibilities. Knowledge is still being sought, for example, about the physiological role played by minute quantities of some of the elements found in the body. The ability to determine accurately a few parts per million of "trace e l e m e n t s " in the various tissues and body fluids is expected to provide much useful i n f o r m a t i o n as to the functions of these materials.

Summary A large number of different radioisotopes have been used for measurement of disease conditions in the human body. They may m e a s u r e liquid volumes, r a t e s of flow or r a t e s of transfer through organs or membranes; they may show the behavior of internal organs; they may differentiate between normal and malignant t i s s u e s . Hundreds of hospitals a r e now making thousands of these tests annually. This does not mean that all the diagnostic problems have been solved. Much of the work is on an experimental rather than a routine b a s i s . Improvements in techniques a r e still being made. As quantities of radioisotopes available for these purposes grow, and as the cost continues to drop, it is expected there will be still more applications. Finally, this does not mean we no longer need the doctor's diag-

30

(^

ÂŽ

ÂŽ

A linear photoscanner produced these pictures of (A) a normal thyroid, (B) an enlarged thyroid, and (C) a cancerous thyroid.

cancer m e t a s t a s e s , brain tumors, and the size, shape, and activity of the thyroid gland. Because of its unique connection with the thyroid gland, iodine-131 is most valuable in m e a s u r e m e n t s connected with that organ. Thyroxin, an iodine compound, is manufactured in the thyroid gland, and t r a n s f e r r e d by the blood s t r e a m to the body t i s s u e s . The thyroxin helps to govern the oxygen consumption of the body and therefore helps control its metabolism. Proper production of thyroxin is essential to the proper utilization of nutrients. Lowered metabolism means increased body weight. Lowered thyroid activity may mean expansion of the gland, causing one form of goiter. Iodine-131 behaves in the body just as the natural nonradioactive isotope, iodine-127, does, but the radioactivity p e r m i t s observation from outside the body with some form of radiation counter. Iodine can exist in the body in many different chemical compounds, and the counter can tell where it is but not in what form. Hence chemical manipulation is n e c e s s a r y in applying this technique to different diagnostic p r o c e d u r e s . The thyroid gland, which is located at the base of the neck, is very efficient in trapping inorganic iodide from the blood s t r e a m , concentrating and storing the iodinecontaining m a t e r i a l and gradually releasing it to the blood s t r e a m in the form of protein-bound iodine (PBI). One of the common diagnostic procedures for d e t e r m i n ing thyroid function, therefore, is to m e a s u r e the p e r c e n t age of an administered dose of '^h that is taken up by the gland. Usually the patient is given a very small dose of radioactive sodium iodide solution to drink, and two hours later the amount of iodine in the gland is determined by measuring the radiation coming from the neck a r e a . In

19


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tp'^rv^'^

Still another common m e a s u r e m e n t using C r - l a b e l e d r e d blood cells is the determination of the amount and location of bleeding from the gastrointestinal tract (the stomach and bowels). The amount is found by simple m e a s u r e m e n t of chromium in the blood that appears in the stools. To find the location is slightly m o r e complicated. The intestinal contents a r e sampled at different levels through an inserted tube, and the radiation of the samples d e t e r mined separately. Finally, gastrointestinal loss of protein can be measured with the aid of ^'Cr-labeled blood s e r u m . The s e r u m is treated with CrClg and then injected into a vein. In s e v e r a l very serious ailments there is serious loss of blood p r o tein through the intestines. In these conditions the ^'Cr level in the intestinal excretions is high, and this a l e r t s the doctor to apply remedial m e a s u r e s .

Cobalt-60 Vitamin B12 is a cobalt compound. Normally the few milligrams of B12 in the body a r e stored in the liver and released to the blood s t r e a m as needed. In pernicious anemia, a potentially fatal but curable disease, the B12 content of the blood falls from the usual level of 3 0 0 - 9 0 0 m i c r o m i c r o g r a m s per milliliter (ml) to 0 to 100 m i c r o m i c r o g r a m s per ml. The administration of massive doses of B12 i s the only known remedy for this condition. If the B12 is labeled with radioactive cobalt, its passage into the blood s t r e a m may be observed by several different methods. The simplest is to give the B12 by mouth, and after about 8 hours study the level of cobalt radioactivity in the blood. Cobalt-60 has been used for s e v e r a l y e a r s , but recently cobalt-58 has been found more satisfactory. It has a half-life of 72 days while ^"Co has a 5.3-year halflife. This reduces greatly the amount of radiation to the patient's liver by the retained radioactivity.

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nostic skill. All radioisotope p r o c e d u r e s a r e m e r e l y tools to aid the skilled physician. As the practice of medicine has changed from an a r t to a science, radioisotopes have played a useful part.

THERAPY A Successful Case A doctor recently told this story about a cancer patient who was cured by irradiation with cobalt-60. " A 75-year-old white male patient, who had been hoarse for one month, was treated unsuccessfully with the usual medications given for a bad cold. Finally, examination of his larynx revealed an ulcerated swelling on the right vocal cord. A biopsy (microscopic examination of a tissue sample) was made, and it was found the swelling was a squamous-cell cancer. "Daily radiation treatment using a cobalt-60 device was started and continued for 31 days. This was in September 1959. The cobalt-60 unit is one that can be operated by remote control. It positions radioactive cobalt over a collimator, which determines the size of the radiation beam reaching the patient. The machine may be made to rotate around the patient or can be used at any desired angle or position.

Iodine-131 Like chromium-51, iodine is a versatile t r a c e r element. It is used to determine blood volume, cardiac output, plasma volume, liver activity, fat metabolism, thyroid

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"when the treatment s e r i e s was in p r o g r e s s , the patient's voice was temporarily made worse, but it returned to normal within two months after the treatment ended. The radiation destroyed the cancerous growth, and frequent examinations over 6 y e a r s since have failed to reveal any regrowth. "The treatment spared the patient's vocal cords, and his voice, airway, and food passage w e r e p r e s e r v e d . " This dramatic tale with a happy ending is a good one with which to s t a r t a discussion of how doctors use r a d i o isotopes for treatment of d i s e a s e .

General Principles Radioisotopes have an important role in the treatment of disease, particularly cancer. It is still believed that cancer is not one but s e v e r a l d i s e a s e s with possible multiple causes. Great p r o g r e s s is being made in development of chemicals for relief of cancer. Nevertheless, radiation and surgery a r e still the main methods for treating cancer, and there a r e many conditions in which relief can be obtained through use of radiation. Moreover, the imaginative use of radioisotopes gives much g r e a t e r flexibility in r a d i ation therapy. This is expected to be true for some y e a r s to come even as p r o g r e s s continues. Radioisotopes s e r v e as concentrated s o u r c e s of radiation and frequently a r e localized within the diseased cells or organs. The dose can be computed to yield the maximum therapeutic effect without harming adjacent healthy t i s s u e s . Let us see some of the ways in which this is done.

Iodine-131 and Iodine-132 Iodine, as was mentioned e a r l i e r , concentrates in the thyroid gland, and is converted there to protein-bound iodine that is slowly released to the blood s t r e a m . Iodine131, in concentrations much higher than those used in diagnostic tests, will i r r a d i a t e thyroid cells, thereby damage them, and reduce the activity of an overactive thyroid (hyperthyroidism). The energy is released within the affected gland, and much of it is absorbed t h e r e . Iodine-131 has a half-life of 8.1 days. In contrast, '^^I has

32

In this cardiac output study a probe is positioned over the heart and the passage of iodine-131 labeled human sermn albumin through this area is recorded.

r e q u i r e s that a radiation counter be mounted on the outside of the chest over the aorta (main a r t e r y leaving the heart). A sample of labeled red blood cells is introduced into a vein, and the recording device counts the radioactivity appearing in the aorta as a function of time. Eventually, of course, the counting r a t e (the number of radioactive d i s integrations per second) levels off when the indicator s a m ple has become mixed uniformly in the blood s t r e a m . F r o m the shape of the curve on which the data a r e recorded during the m e a s u r e m e n t s taken before that time, the operator calculates the h e a r t output per second. Obstetricians caring for expectant mothers use red cells tagged with ^'Cr to find the exact location of the placenta. For example, in the condition known as placenta previa, the placenta — the organ within the uterus by which nourishment is transferred from the m o t h e r ' s blood to that of the unborn child — may be placed in such a position that fatal bleeding can occur. A radiation-counting instrument placed over the lower abdomen gives information about the exact location of the placenta. If an abnormal situation exists, the attending physician is then alert and ready to cope with it. The advantages of chromium over iodine-131, which has also been used, a r e that smaller doses a r e required, and that there is no transfer of radioactivity to the fetal circulation.

17


\

some of them are injected back into the patient and an identical sample is injected into a compatible normal individual. If the t r a c e r shows that the cells' survival time is too short in both recipients to the same degree, the conclusion IS that the r e d cells themselves must be abnormal. On the other hand, if the cell-survival time is normal in the normal individual and too short in the patient, the diagnosis is that the patient's blood contains some substance that d e stroys the red cells. When chromium trichloride, CrCls, is used as the tagging agent, the chromium is bound almost exclusively to plasma proteins, r a t h e r than the red cells. Chromium-51 may thus be used for estimating the volume of plasma c i r c u lating in the heart and blood v e s s e l s . The same type of computation is carried on for red cells (after correction for a small amount of chromium taken up by the red blood cells). This procedure is easy to c a r r y out because the radioactive chromium chloride is injected directly into a vein. An ingenious automatic device has been devised for computing a patient's total blood volume using the ^^Cr measurement of the red blood cell volume as its b a s i s . This determination of total blood volume is of course necessary in deciding whether blood or plasma t r a n s fusions a r e needed in c a s e s involving bleeding, burns, or surgical shock. This ^'Cr procedure was used during the Korean War to determine how much blood had been lost by wounded patients, and helped to save many, many lives. For several y e a r s , iodine-131 has been used as a t r a c e r in determining cardiac output, which is the r a t e of blood flow from the heart It has appeared recently that red blood cells tagged with ^'Cr a r e more satisfactory for this measurement than iodine-labeled albumin in the blood s e r u m It is obvious that the blood-flow r a t e is an extremely important physiological quantity, and a doctor must know it to t r e a t either heart ailments or circulatory d i s turbances. In contrast to the iodine-131 procedure, which r e q u i r e s that an a r t e r y be punctured and blood samples be removed regularly for measurement, chromium labeling merely

16

a half-Me of only 2.33 hours. What this means is that the s a m e weight of radioactive '^^I will give a g r e a t e r radiation dose than '^'l would, and lose its activity rapidly enough to present much l e s s hazard by the time the iodine is r e leased to the blood s t r e a m . Iodine-132 i s therefore often p r e f e r r e d for treatment of this s o r t .

Boron-10 Boron-lO has been used experimentally in the treatment of inoperable brain tumors. Glioblastoma multiforme, a particularly malignant form of cancer, is an invariably fatal disease in which the patient has a probable life expectancy of only 1 y e a r . The tumor extends roots into normal t i s s u e s to such an extent that it is virtually i m possible for the surgeon to remove all malignant tissue even if he removes enough normal brain to affect the functioning of the patient seriously. With or without operation the patient dies within months. This is therefore a case in which any improvement at all i s significantly helpful. The blood-bram b a r r i e r that was mentioned e a r l i e r minimizes the passages of many m a t e r i a l s into normal brain t i s s u e s . But when some organic or inorganic compounds, such as the boron compounds, a r e injected into the blood s t r e a m , they will pass readily into brain tumors and not move into normal brain cells. Boron-10 absorbs slow neutrons readily, and becomes boron-11, which disintegrates almost immediately into alpha p a r t i c l e s and a lithium isotope. Alpha p a r t i c l e s , r e m e m b e r , have very little penetrating power, so all the energy of the alpha radioactivity is expended within the individual tumor cells. This is an ideal situation, for it makes possible destruction of tumor cells with virtually no harm to normal cells, even when the two kinds a r e closely intermingled. Slow neutrons pass through the human body with very little damage, so a fairly strong dose of them can be safely applied to the head. Many of them will be absorbed by the boron-10, and maximum destruction of the cancer will occur, along with minimum hazard to the patient. This treatment is accomplished by placing the head of the patient in a beam of slow neutrons emerging from a nuclear r e -

33


scintillation counters, one mounted on each side of the patient's head. The electrical circuitry in the scanner i s such that only those gamma r a y s a r e counted that impinge simultaneously on both counters. This procedure eliminates most of the "noise", or scattered and background radiation.

Chromium-51

Because chromium, in the molecule sodium chromate, attaches itself to red blood cells, it is useful in s e v e r a l kinds of t e s t s . The procedures a r e slightly complicated, but yield useful information. In one, a sample of the patient's blood is withdrawn, stabilized with heparin (to prevent clotting) and incubated with a t r a c e r of radioactive sodium chromate. Excess chromate that is not taken up by the cells is reduced and washed away. Then the radioactivity of the cells is measured, just before injection into the patient. After a suitable time to permit thorough mixing of the added m a t e r i a l throughout the blood s t r e a m , a new blood sample is taken and its radioactivity is measured. The total volume of red blood cells then can be calculated by dividing the total radioactivity of the injected sample by the activity per milliliter of the second sample. In certain types of anemia the patient's red blood cells die before completing the usual r e d - c e l l lifetime of about 120 days. To diagnose this, red cells a r e tagged with chromium-51 (^^Cr) in the manner just described. Then

Spleen scans made with red blood cells, which had been altered by heat treatment and tagged with chromium-51. Such damaged cells are selectively removed by the spleen. A is a normal spleen. B shows an abscess m the spleen. Note dark ring of radioactivity surrounding the lighter area of decreased activity at the central portion of spleen.

15


them, some may use even m o r e . In any case they a r e merely tools to augment the doctors' skill. Examples of measurements t h a t can be made include blood volume, blood circulation rate, red blood cell turnover, glandular activity, location of cancerous tissue, and r a t e s of formation of bone tissue or blood cells. Of the more than 100 different radioisotopes that have A differential multi-detector debeen used by doctors during veloped at Brookhaven National the past 30 y e a r s , five have Laboratory locates brain tumors received by far the greatest with positron-emitting isotopes. By using many pairs of detection attention. These a r e iodinecrystals, the device shortens the 131, phosphorus-32, gold-198, scanning time and increases acchromium-51, a n d iron-59. curacy. (See cover for another type of positron scanner.) Some others have important u s e s , too, but have been l e s s widely employed than these five. The use of individual r a dioisotopes in making important diagnostic tests makes a fascinating story. Typical instances will be described in the following pages.

Arsenic-74 Brain tumors tend to concentrate certain ions (charged atoms or molecules). When these ions a r e g a m m a - r a y emitters, it is possible to take advantage of the penetrating power of their gamma r a y s to locate the tumor with a scanning device located outside the skull. Arsenic-74 and copper-64 a r e isotopes emitting positrons,* which have one peculiar property. Immediately after a positron is emitted from a nucleus it decays, p r o ducing two gamma r a y s that travel in exactly opposite directions. The scanning device has two detectors called *A positron is an "antielectron' but a positive charge.

W

It has the mass of an electron

actor a few minutes after the boron-10 compound has been injected into a vein. The difficulty is that most boron compounds themselves a r e poisonous to human tissues, and only small concentrations can be tolerated in the blood. Efforts have been made, with some s u c c e s s , to synthesize new boron compounds that have the g r e a t e s t possible degree of selective absorption by the t u m o r s . Both organic and inorganic compounds have been tried, and the degree of selectivity has been shown to be much g r e a t e r for some than for o t h e r s . So far it is too early to say that any c u r e s have been brought about, but r e s u l t s have been very encouraging. The ideal drug, one which will make possible complete destruction of the cancer without harming the patient, is probably still to be devised.

Phosphorus-32 Another disease which is peculiarly open to attack by radioisotopes is polycythemia vera. This is an insidious ailment of a chronic, slowly progressive nature, characterized by an abnormal i n c r e a s e in the number of r e d blood cells, an increase in total blood volume, enlargement of the spleen, and a tendency for bleeding to occur. There is some indication that it may be related to leukemia. Until recent y e a r s there was no very satisfactory t r e a t ment of this malady. The ancient practice of bleeding was as useful as anything, giving temporary relief but not striking at the underlying cause. There is still no true cure, but the use of phosphorus-32 has been very effective in causing disappearance of symptoms for periods from months to y e a r s , lengthening the patient's life considerably. The purpose of the ^^P treatment (using a sodium-radiophosphate solution) is not to destroy the excess of red cells, a s had been tried with some drugs, but r a t h e r to slow down their formation and thereby get at the basic cause. Phosphorus-32 emits pure beta r a y s having an average path in tissue only 2 m i l l i m e t e r s long. Its half-life is 14.3 days. When it is given intravenously it mixes rapidly with the circulating blood and slowly accumulates in tissues that utilize phosphates in their metabolism. This brings 35


Lamps

Thyroid surgery patient 4 days after 5 mc dose of

I

Motor synchronized y with scanner -^

Composite of 10 films

appreciable concentration in the blood-forming tissues (about twice as much inbloodcells a s m general body cells). One other pertinent fact is that these rapidly dividing hematopoietic cells a r e extremely sensitive to radiation. (Hematopoietic cells a r e those that a r e actively forming

Scintillation counters

100 No cases 201 Average age 52 Median survival . . 1 3 2 . Survival for C

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5 years

91 5°

10 years

70 0°

^ 50 u u ID Q.

Survival of polycythemia vera patients after ^^P therapy.

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15

^ 20

25

Years

blood cells and are therefore those that should be attacked selectively.) The dose required is of course many times that needed for diagnostic studies, and careful observation of the r e s u l t s is necessary to determine that exactly the desired effect has been obtained. There exists some controversy over this course of treatment. No one denies that the lives of patients have been lengthened notably. Nevertheless since the purpose of the procedure is to reduce red cell formation, there exists the hazard of too great a reduction, and the possibility of causing leukemia (a disease of too few red cells). There

36

The first whole body scanner, which was developed at the Donner Laboratory m 1952 and is still being used. The lead collimator contains 10 scintillation counters and moves across the subject. The bed is moved and serial scans are made and then joined together to form a head-to-toe picture of the subject. The diagram shows a scan and the parts of a scanner. (Also see page 21.)

13


may be a small i n c r e a s e in the number of c a s e s of leukemia among those treated with ^^P compared with the general population. The controversy a r i s e s over whether the ^^P treatment caused the leukemia, or whether it merely p r o longed the lives of the patients until leukemia appeared as it would have in these persons even without treatment. This is probably quibbling, and many doctors believe that the slight unproven r i s k i s worth taking to produce the admitted lengthy freedom from symptoms.

Gold-198

The inset picture shows a brain scan made with a positron scintillation camera. A tumor is indicated by light area above ear. (Light area in facial region is caused by uptake in bone and extracellular space.) The photograph shows a patient, completely comfortable, receiving a brain scan on one of the three rectilinear scanning devices in the nuclear medicine laboratory of a hospital.

The last ailment we shall discuss in this section is the accumulation of large quantities of excess fluid in the chest and abdominal cavities from their linings, as a consequence of the growth of certain types of malignant tumors. Frequent surgical drainage was at one time the only very useful treatment, and of course this was both uncomfortable and dangerous. The use of radioactive colloidal suspensions, p r i m a r i l y colloidal gold-198, has been quite successful in palliative treatment: It does not cure, but it does give marked relief. Radioactive colloids (a colloid is a suspension of one very finely divided substance in some other medium) can be introduced into the abdominal cavity, where they may

Mr. P e t e r s , who admitted to no pain or other adverse reaction from the scanning, was photographed by the scanner from the front and both sides. The procedure took l e s s than an hour. The developed film showed that the technetium had concentrated in one spot, indicating definitely that a tumor was present. Comparison of front and side views made it possible to pinpoint the location exactly. Surgery followed to remove the tumor. Today, thanks to sound and early diagnosis, Mr. P e t e r s is well and back on the job. His case is an example of how radioisotopes a r e used in hospitals and medical centers for diagnosis. In one representative hospital, 17 different kinds of r a dioisotope measurements a r e available to aid physicians in making their diagnoses. All the methods use t r a c e r quantities of m a t e r i a l s . Other hospitals may use only a few of

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r e m a i n suspended or settle out upon the lining. In either case, since they a r e not dissolved, they do not pass through the membranes or cell walls but remain within the cavity. Through its destructive and retarding effect on the cancer cells the radiation inhibits the oozing of fluids. Gold-198 offers s e v e r a l advantages in such c a s e s . It has a short half-life (2.7 days); it is chemically inert and therefore nontoxic; and it emits beta and gamma radiation that is almost entirely absorbed by the tissues in its i m mediate neighborhood. The r e s u l t s have been very encouraging. There is admittedly no evidence of any c u r e s , or even lengthening of life, but there has been marked reduction of discomfort and control of the oozing in over two-thirds of the cases treated.

Their effects a r e analogous to those from the radiation that every one of us continually r e c e i v e s from natural s o u r c e s within and without the body. Therapeutic doses — those given for medical t r e a t m e n t — b y contrast, a r e given to patients with a disease that is in need of control, that is, the physician d e s i r e s to destroy selectively cells or tissues that a r e abnormal. In these c a s e s , therefore, the skill and experience of the attending physician must be applied to limit the effects to the desired benefits, without damage to healthy organs. This booklet i s devoted to these two functions of r a d i o isotopes, diagnosis and therapy; the field of medical r e s e a r c h using radioactive tools is so large that it r e q u i r e s s e p a r a t e coverage.*

Beads, Needles, and Applicators

DIAGNOSIS

Radium salts were the first m a t e r i a l s to be used for radiation treatment of cancer. Being both very expensive and very long-lived, they could not be injected but were used in temporary implants. Radium salts in powder form w e r e packed into tiny hollow needles about 1 centimeter long, which w e r e then sealed tightly to prevent the escape of radon gas. As radium decays (half-life 1620 years) it becomes gaseous radon. The latter is also radioactive, so it must be prevented from escaping. These gold needles could be inserted into tumors and left there until the d e s i r e d dosage had been administered. One difficulty in radium treatment was that the needles were so tiny that on numerous occasions they were lost, having been thrown out with the d r e s s i n g s . Then, both because of their value and their hazard, a frantic search ensued when this happened, not always ending successfully. The fact that radon, the daughter of radium, is constantly produced from its parent, helped to eliminate some of this The needle used for implantation of yttrium-90 pellets into the pituitary gland is shown in the top photograph. In the center X ray the needle is in place and the pellets have just been passed through it into the bone area surrounding the pituitary gland. The bottom X ray shows the needle withdrawn and the pellets within the bone.

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Pinpointing Disease Mr. P e t e r s , 35-year-old father of four and a resident of Chicago's northwest side, went to a Chicago hospital one winter day after p e r s i s t e n t headaches had made his life m i s e r a b l e . Routine examinations showed nothing a m i s s and his doctor ordered a " b r a i n s c a n " in the hospital's department of nuclear medicine. Thirty minutes before " s c a n time", Mr. P e t e r s was given, by intravenous injection, a minute amount of r a dioactive technetium. This radiochemical had been s t r u c tured so that, if t h e r e w e r e a tumor in his cranium, the radioisotopes would be attracted to it. Then he was positioned so an instrument called a scanner could pass close to his head. As the motor-driven scanner passed back and forth, it picked up the gamma r a y s being emitted by the r a d i o active technetium, much a s a Geiger counter detects other radiation. These r a y s were recorded as black blocks on sensitized film inside the scanner. The r e s u l t was a piece of exposed film that, when developed, bore an architectural likeness or image of Mr. P e t e r ' s cranium. *See Radioisotopes and Life Processes, another booklet in this series, for a discussion of one area of biomedical research.

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With one conspicuous exception, it is impossible for a chemist to distinguish any one atom of an element from another. Once ordinary salt gets into the blood s t r e a m , for example, it normally has no characteristic by which anyone can decide what its source was, or which sodium atoms were added to the blood and which were already present. The exception to this is the case in which some of the atoms a r e "tagged" by being made radioactive. Then the radioactive atoms a r e readily identified and their quantity can be measured with a counting device. A radioactive t r a c e r , it is apparent, corresponds in chemical nature and behavior to the thing it t r a c e s . It is a true p a r t of it, and the body t r e a t s the tagged and untagged m a t e r i a l in the s a m e way. A molecule of hemoglobin carrying a radioactive iron atom is still hemoglobin, and the body p r o c e s s e s affect it just as they do an untagged hemoglobin molecule. The difference is that a scientist can use counting devices to follow the t r a c e r molecules wherever they go. It should be evident that t r a c e r s used in diagttosis—to identify disease or improper body function—are p r e s e n t in such small quantities that they a r e relatively h a r m l e s s .

One of the first scans made by a photoscanner. The photorecording (dark bands), superimposed on an X-ray picture Jor orientation, shows radioactivity m a cancer m the patient's neck.

10


difficulty. Radium could be kept in solution, decaying constantly to yield radon. The latter, with a half-life of 4 days, could be sealed into gold seeds 3 by 0.5 m i l l i m e t e r s and left in the patient without much risk, even if he failed to r e t u r n for its removal at exactly the appointed time. The cost was low even if the seeds were lost. During the last 20 y e a r s , other highly radioactive sources have been developed that have been used successfully. Cobalt-60 is one popular m a t e r i a l . Cobalt-59 can be neutron-irradiated in a reactor to yield cobalt-60 with such a high specific activity that a small cylinder of it is m o r e radioactive than the entire world's supply of radium. Cobalt-60 has been encapsulated in gold or silver needles, sometimes of special shapes for adaptation to specific tumors such a s carcinoma of the cervix. Sometimes needles have been spaced at intervals on plastic ribbon that adapts itself readily to the shape of the organ treated. Gold-198 is also an interesting isotope. Since it i s chemically inert in the body, it needs no protective coating, and as is the case with radon, its short half-life makes its u s e simpler in that the time of removal is not of critical importance. Ceramic beads made of yttrium-90 oxide a r e a m o d e r ately new development. One very successful application of this m a t e r i a l has been for the destruction of the pituitary gland. Cancer may be described a s the runaway growth of cells. The secretions of the pituitary gland s e r v e to stimulate cell reproduction, so it was reasoned that destruction of this gland might well slow down growth of a tumor e l s e where in the body. The trouble was that the pituitary is small and located at the base of the brain. Surgical r e moval had brought dramatic relief (not cure) to many patients, but the surgery itself was difficult and hazardous. Tiny yttrium-90 oxide beads, glasslike in nature, can be implanted directly in the gland with much l e s s difficulty and risk, and do the work of destroying the gland with little damage to its surroundings. The key to the s u c c e s s of yttrium-90 is the fact that it is a b e t a - e m i t t e r , and beta r a y s have so little penetrating power that their effect is limited to the immediate a r e a of the implant.

40

In one way or another, the key to the usefulness of r a d i o isotopes lies in the energy of the radiation. When radiation is used for treatment, the energy absorbed by the body is used either to destroy tissue, particularly cancer, or to s u p p r e s s some function of the body. Properly calculated and applied doses of radiation can be used to produce the desired effect with minimum side reactions. Expressed in t e r m s of the usual work or heat units, ergs or calories, the amount of energy associated with a radiation dose is small. The significance lies in the fact that this energy is released in such a way as to produce important changes in the molecular composition of individual cells within the body.

What Do We Mean by Tracer Atoms? When a radioisotope is used as a t r a c e r , the energy of the radiation t r i g g e r s the counting device, and the exact amount of energy from each disintegrating atom is m e a sured. This differentiates the substance being traced from other materials naturally present.

This is the first photoscanner, which was developed in 1954 at the University of Pennsylvania and was retired from service in 1963. When gamma rays emitted by a tracer isotope in the patient's body struck the scanner, a Slashing light produced a dot on photographic film. The intensity of the light varied with the counting rate and thus diseased tissues that differed little from normal tissue except in their uptake of an isotope could be discerned.

9


diagnosis, and radiant-energy e m i t t e r s a r e used for t r e a t ment (therapy). Radioisotopes offer two advantages. F i r s t , they can be used in extremely small amounts. As little as one-billionth of a gram can be measured with suitable apparatus. Secondly, they can be directed to various definitely known p a r t s of the body. For example, radioactive sodium iodide behaves in the body just the s a m e as normal sodium iodide found in the iodized salt used in many homes. The iodine concentrates in the thyroid gland where it is converted to the hormone thyroxin. Other radioactive, or "tagged", atoms can be routed to bone marrow, red blood cells, the liver, the kidneys, or made to remain in the blood s t r e a m , where they a r e measured using suitable instruments.* Of the three types of radiation, alpha particles (helium nuclei) a r e of such low penetrating power that they cannot be used for measurement from outside the body. Beta particles (electrons) have a moderate penetrating power, therefore they produce useful therapeutic r e s u l t s in the vicinity of their r e l e a s e , and they can be detected by sensitive counting devices. Gamma r a y s a r e highly energetic, and they can be readily detected by counters — radiation measurement d e v i c e s — u s e d outside the body.

Particle or ray Alpha

Paper

Wood

Teletherapy Over 200 teletherapy units a r e now in use in the United States for treatment of patients by using very high intensity s o u r c e s of cobalt-60 (usually) or cesium-137. Units c a r r y ing s o u r c e s with intensities of m o r e than a thousand curies a r e common. Since a curie is the amount of radioactivity in a g r a m of radium that is in equilibrium with its decay products, a 1000-curie s o u r c e is comparable to 2 pounds of pure radium. Neglecting for the moment the scarcity and enormous cost of that much radium (millions of dollars), we

Concrete

I

Beta Gamma

y Relative

penetration

of alpha, beta, and gamma

radiation.

For comparison, a sheet of paper stops alpha p a r t i c l e s , a block of wood stops beta p a r t i c l e s , and a thick concrete wall stops gamma r a y s .

*See Appendix for a description of types of radiation-detection instruments.

8

The cobalt-60 unit at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, employs a 3000-curie source. This unit has a mechanism that alloiisfor rotation therapy about a stationary patient. Many different treatment positions are possible. This patient, shown in position for therapy, has above her chest an auxiliary diaphragm that consists of an expanded metal tray on which blocks of either tungsten or lead are placed to absorb gamma rays and thus shape the field of treatment. In this case they allow for irradiation of the portions of the neck and chest delineated by the lines visible on the patient.

41


have to consider that it would be large in volume and consequently difficult to apply. Radiation from such a quantity cannot be focussed; consequently, either much of it will fall upon healthy tissue surrounding the cancer or much of it will be wasted if a narrow passage through the shield is aimed at the tumor. In contrast, a tiny cobalt source p r o vides just as much radiation and more if it can be brought to bear upon the exact spot to be treated. Most interesting of all is the principle by which internal cancers can be treated with a minimum of damage to the skin. Deep x-irradiation has always been the approved treatment for deep-lying c a n c e r s , but until recently this required very cumbersome units. With the modern r o t a tional device shown in the diagram, a very narrow beam is aimed at the patient while the source is mounted upon

HALF-LIFE PATTERN OF STRONTIUM-90

Beginning

1 Half-life

2 Half-lives

3 Half-lives

4 Half-lives

of Life

28 years

56 years

84 years

112 years

Most artificially made radioisotopes have relatively short half-lives. This makes them useful in two ways. F i r s t , it means that very little m a t e r i a l is needed to obtain a significant number of disintegrations. It should be evident that, with any given number of radioactive atoms, the number of disintegrations per second will be inversely proportional to the half-life. Second, by the time 10 halflives have elapsed, the number of disintegrations per s e c ond will have dwindled to V-[02i th^ original number, and the amount of radioactive m a t e r i a l is so small it is usually no longer significant. (Note the decrease in the figure above.)

How Are Radioisotopes Used? a c a r r i e r that revolves completely around him. The patient is positioned carefully so that the lesion to be treated is exactly at the center of the circular path of the c a r r i e r . The result is that the beam s t r i k e s its internal target during the entire circular orbit, but the same amount of radiation is spread out over a belt of skin and tissue all the way around the patient. The damage to any one skin cell is minimized. The advantage of this device over an e a r l i e r device, in which the patient was revolved in a stationary beam, is that the mechanical equipment is much simpler.

42

A radioisotope may be used either as a source of r a d i a tion energy (energy is always released during decay), or as a t r a c e r : an identifying and readily detectable m a r k e r m a t e r i a l . The location of this material during a given treatment can be determined with a suitable instrument even though an unweighably small amount of it is present in a mixture with other m a t e r i a l s . On the following pages we will discuss medical u s e s of individual radioisotopes — first those used as t r a c e r s and then those used for their energy. In general, t r a c e r s a r e used for analysis and

7


What Are Radioisotopes? In the 19th Century an Englishman, John Dalton, put forth his atomic theory, which stated that all atoms of the same element were exactly alike. This remained unchallenged for 100 y e a r s , until experiments by the British chemist, Frederick Soddy, proved conclusively that the element neon consisted of two different kinds of Frederick Soddy atoms. All were alike in chemical behavior but some had an atomic weight (their m a s s relative to other atoms) of 20 and some a weight of 22. He coined the word isotope to describe one of two or m o r e atoms having the same atomic number but different atomic weights.* Radioisotopes a r e isotopes that a r e unstable, or radioactive, and give off radiation spontaneously. Many r a d i o isotopes a r e produced by bombarding suitable targets with neutrons now readily available inside atomic r e a c t o r s . Some of them, however, a r e more satisfactorily created by the action of protons, deuterons, or other subatomic p a r ticles that have been given high velocities in a cyclotron or similar accelerator. Radioactivity is a p r o c e s s that is practically uninfluenced by any of the factors, such a s temperature and p r e s s u r e , that a r e used to control the rate of chemical reactions. The r a t e of radioactive decay appears to be affected only by the s t r u c t u r e of the unstable (decaying) nucleus. Each radioisotope has its own half-life, which is the time it takes for one half the number of atoms present to decay. These half-lives vary from fractions of a second to millions of y e a r s , depending only upon the atom. We shall s e e that the half-life is one factor considered in choosing a particular isotope for certain u s e s .

*An equivalent statement is that nuclei of isotopes have the s a m e number of protons but different numbers of neutrons.

6

CONCLUSIONS In summary, then, we may say that radioisotopes play an important role in medicine. For the diagnostician, small h a r m l e s s quantities of many isotopes s e r v e a s tools to aid him in gaining information about normal and abnormal life p r o c e s s e s . The usefulness of this information depends upon his ingenuity in devising questions to be answered, apparatus to measure the r e s u l t s , and explanations for the r e s u l t s . For therapeutic u s e s , on the other hand, the important thing to r e m e m b e r i s that radiation damages many kinds of cells, especially while they a r e in the p r o c e s s of division (reproduction)."*^ Cancer cells a r e self-reproducing cells, but do so in an uncontrolled manner. Hence cancer cells are particularly vulnerable to radiation. This treatment r e quires potent sources and correspondingly i n c r e a s e s the hazards of u s e . In all c a s e s , the use of these potentially hazardous m a t e r i a l s belongs under the supervision of the U. S. Atomic Energy Commission.t Licenses a r e issued by the Commission after investigation of the training, ability, and facilities possessed by prospective u s e r s of dangerous quantities. At regular intervals courses a r e given to train individuals in the techniques necessary for safe handling, and graduates of these c o u r s e s are now located in laborat o r i e s all over the country. The future of this field cannot be predicted with certainty. Research in hundreds of laboratories is continuing to add to our knowledge, through new apparatus, new techniques, and new experiments. Necessarily the number of totally new fields is becoming s m a l l e r , but most certainly the number of cases using procedures already established is bound to i n c r e a s e . We foresee steady improvement and growth in all u s e s of radioisotopes in medicine.

*See Your Body and Radiation and The Genetic Effects of Radiation, other booklets in this s e r i e s , for detailed explanations of radiation effects. tThe use of radium is not under AEC control.

43


APPENDIX Measuring Instruments* The measurement of radioactivity must be accomplished indirectly, so use is made of the physical, chemical, and e l e c t r i c a l effects of radiation on m a t e r i a l s . One commonly used effect is that of ionization. Alpha and beta particles ionize gases through which they p a s s , thereby making the g a s e s electrically conductive. A family of counters u s e s this principle- the ionization chamber, the proportional counter, and the Geiger-Miiller counter. Certain c r y s t a l s , sodium iodide being an excellent example, emit flashes of visible light when struck by ionizing radiation. These crystals a r e used in scintillation counters.

Ionization Chambers One of a pair of electrodes is a wire located centrally within a cylinder. The other electrode is the wall of the chamber. Radiation ionizes the gas withm the chamber, permitting the passage of current between the electrodes. The thickness of a window in the chamber wall determines the type of radiation it can m e a s u r e . Only gamma r a y s will pass through a heavy metal wall, glass windows will admit all gammas and most betas, and plastic (Mylar) windows a r e n e c e s s a r y to admit alpha p a r t i c l e s . Counters of this type, when properly calibrated, will m e a s u r e the total amount of radiation received by the body of the w e a r e r .

Proportional Counters This of the energy record rays.

IS a type of ionization chamber in which the intensity electrical pulse it produces is proportional to the of the incoming particle. This makes it possible to alpha particles and discriminate against gamma

*One family of measuring instruments is described in Whole Body Counters, another booklet in this series. These are large devices that make use of scintillating crystals or liquids.

44

Patient application of these new s o u r c e s of bombarding p a r t i c l e s resulted m the creation of small quantities of hundreds of radioactive isotopic s p e c i e s , each with d i s tinctive c h a r a c t e r i s t i c s . In turn, as we shall see, many ways to use radioisotopes have been developed in medical therapy, diagnosis, and r e s e a r c h . By now, more than 3000 hospitals hold licenses from the Atomic Energy Commission to use radioisotopes. In addition, many thousands of doctors, dentists, and hospitals have X - r a y machines that they use for some of the same broad p u r p o s e s . One of the results of all this is that every month new u s e s of radioisotopes a r e developed. More persons are trained every y e a r in methods of radioisotope use and more manufacturers are producing and packaging radioactive m a t e r i a l s . This booklet tells some of the s u c c e s s e s achieved with these m a t e r i a l s for medical purposes.

What Is Radiation? Radiation is the propagation of radiant energy in the form of waves or p a r t i c l e s . It includes electromagnetic radiation ranging from radio waves, infrared heat waves, visible light, ultraviolet light, and X rays to gamma r a y s . It may also include b e a m s of particles of which electrons, positrons, neutrons, protons, deuterons, and alpha p a r t i c l e s are the best known. *

What Is Radioactivity? It took several y e a r s following the basic discovery by Becquerel, and the work of many investigators, to s y s t e m atize the information about this phenomenon. Radioactivity IS defined as the property, possessed by some m a t e r i a l s , of spontaneously emitting alpha or beta p a r t i c l e s or gamma r a y s as the unstable (or radioactive) nuclei of their atoms disintegrate.

*For detailed descriptions of these waves and particles, see Our Atomic World, a companion booklet m this series.


Geiger-Miiller Counters These have been widely used and a r e versatile in their applications. The potential difference between the electrodes in the Geiger-Miiller tube (similar to an ionization chamber) is high. A single alpha or beta particle ionizes some of the gas within the chamber. In turn these ions strike other gas molecules producing secondary ionization. The r e s u l t is an "avalanche" or high-intensity pulse of e l e c tricity passing between the electrodes. These pulses can be counted electrically and recorded on a meter at r a t e s up to s e v e r a l thousand per minute. Frederic

and Irene

Joliot-Curie

The next momentous advance was made by F r e d e r i c Joliot, a French chemist who m a r r i e d Irene Curie, daughter of P i e r r e and Marie Curie. He discovered in 1934 that when aluminum was bombarded with alpha p a r t i c l e s * from a radioactive source, emission of positrons (positive electrons) was induced. Moreover, the emission continued long after the alpha source was removed. This was the first example of artificially induced radioactivity, and it stimulated a new flood of discoveries. Frederic and Irene JoliotCurie won the Nobel Prize in chemistry in 1935 for this work. Others who followed this discovery with the development of additional ways to create artificial radioactivity w e r e two Americans, H. Richard Crane and C. C. Lauritsen, the British scientists, John Cockcroft and E. T. S. Walton, and an American, Robert J. Van de Graaff. Ernest O. Lawrence, an American physicist, invented the cyclotron (or "atom s m a s h e r " ) , a powerful source of high-energy particles that induced radioactivity in whatever target materials they i m pinged upon. Enrico F e r m i , an Italian physicist, seized upon the idea of using the newly discovered neutron (an electrically neutral particle) and showed that bombardment with neutrons also could induce radioactivity in a target substance. Cockcroft and Walton, Lawrence, and F e r m i all won Nobel P r i z e s for their work. *AIpha particles are large positively charged particles, identical to helium nuclei. For definitions of unfamiliar words see Nuclear Terms. A Brie] Glossary, SL companion booklet in this s e r i e s .

4

Scintillation Counters Since the development of the photoelectric tube and the photomultiplier tube (a combination of photoelectric cell and amplifier), the scintillation counter has become the most popular instrument for most purposes described in this booklet. The flash of light produced when an individual ionizing particle or r a y s t r i k e s a sodium-iodide c r y s t a l i s noted by a photoelectric cell. The intensity of the flash i s a m e a s u r e of the energy of the radiation, so the voltage of the output of the photomultiplier tube is a m e a s u r e of the wavelength of the original gamma ray. The scintillation counter can observe up to a million counts per minute and discriminate sharply between gamma rays of different ene r g i e s . With proper windows it can be used for alpha or beta counts a s well.

Solid State Counters The latest development i s a tiny silicon (transistor-type) diode detector that can be made as small as a grain of sand and placed within the body with very little discomfort.

Scanners Many of the applications described in this booklet r e quire accurate knowledge of the exact location of the radioactive source within the body. Commonly a detecting tube is used having a collimating shield so that it accepts only that radiation that s t r i k e s it head-on. A motor-driven c a r -

45


r i e r moves the counter linearly at a slow r a t e . Radiation i s counted and whenever the count reaches the p r e d e t e r mined amount — from one count to many — an electric impulse causes a synchronously moving pen to make a dot on a chart. The scanner, upon reaching the end of a line moves down to the next line and s t a r t s over, eventually producing a complete r e c o r d of the radiation sources it has passed over.

Pierre and Marie

Curie

and radium, and showed that they possessed far g r e a t e r radioactivity than uranium itself. For this work Becquerel and the two Curies were jointly awarded the Nobel P r i z e in physics in 1903. At the outset, Roentgen had noticed that although X r a y s passed through human tissue without causing any immediate sensation, they definitely affected the skin and underlying c e l l s . Soon after exposure, it was evident that X r a y s could cause r e d n e s s of the skin, blistering, and even u l ceration, either in single doses or in repeated s m a l l e r doses. In spite of the h a z a r d s * involved, early experim e n t e r s determined that X r a y s could destroy cancer tissues more rapidly than they affected healthy organs, so a basis was established quite soon for one of Medicine's few methods of curing or at least restraining cancer. The work of the Curies in turn stimulated many studies of the effect of radioactivity. It was not long before exp e r i m e n t e r s learned that naturally radioactive elements — like r a d i u m — w e r e also useful in cancer therapy. These elements emitted gamma r a y s , t which a r e like X r a y s but usually a r e even more penetrating, and their application often could be controlled better than X r a y s . Slowly, over the y e a r s , reliable methods were developed for treatment with these radioactive s o u r c e s , and instruments were d e signed for measuring the quantity of radiation received by the patient. *The early dangers from use of X r a y s , due to incomplete understanding and inadequate shielding, have now been eliminated. t Gamma rays a r e high-energy electromagnetic radiation.

46

3


A French physicist, Antome Henri Becquerel, newly appointed to the chair of physics at the Ecole Polytechnique in P a n s , saw that this d i s covery opened up a new field for r e s e a r c h and set to work on some of its ramifications. One of the evident features of the production of X rays was the fact that while they were being created, the glass of the vacHenri Becquerel

""™ ^^^ ^^^^ °^ ^ greemsh phosphorescent glow. This suggested to several physicists that substances which become phosphorescent upon exposure to visible light might give off X rays along with the phosphorescence. Becquerel experimented with this by exposing various c r y s t a l s to sunlight and then placing each of them on a black paper envelope enclosing an unexposed photographic plate. If any X r a y s were thus produced, he reasoned, they would penetrate the wrapping and create a developable spot of exposure on the plate. To his delight, he indeed observed just this effect when he used a phosphorescent m a t e r i a l , uranium potassium sulfate. Then he made a confusing d i s covery. For s e v e r a l days there was no sunshine, so he could not expose the phosphorescent m a t e r i a l . For no particular r e a s o n (other than that there was nothing else to do) Becquerel developed a plate that had been in contact with uranium m a t e r i a l in a dark drawer, even though there had been no phosphorescence. The telltale black spot m a r k ing the position of the mineral nevertheless appeared on the developed plate' His conclusion was that uranium in its normal state gave off X r a y s or something s i m i l a r . At this point, P i e r r e Curie, a friend of Becquerel and also a professor of physics in P a n s , suggested to one of his graduate students, his young bride, M a n e , that she study this new phenomenon. She found that both uranium and thorium possessed this property of radioactivity, but also, surprisingly, that some uranium m i n e r a l s were more radioactive than uranium itself. Through a tedious s e r i e s of chemical separations, she obtained from pitchblende (a uranium ore) small amounts of two new elements, polonium

2

I

SUGGESTED REFERENCES Technical Books Radioactive Isotopes m Medicine and Biology, Solomon Silver, Lea & Febiger, Philadelphia, Pennsylvania 19106, 1962, 347 pp., $8.00. Atomic Medicine, Charles F . Behrens and E. Richard King (Eds.), The Williams & Wilkins Company, Baltimore, Maryland 21202, 1964, 766 pp., $18.00. The Practice oj Nuclear Medicine, William H. Blahd, Franz K. Bauer, and Benedict Casben, Charles C Thomas, Publisher, Springfield, lUinois 62703, 1958, 432 pp., $12.50. Piogtess in Atomic Medicine, John H. Lawrence (Ed.), Grune & Stratton, Inc., New York 10016, 1965, volume 1, 240 pp., $9.75. Radiation Biology and Medicine, VJdlter D. Claus (Ed.), AddisonWesley Publishing Company, Reading, Massachusetts 01867, 1958, 944 pp., $17.50. Part 7, Medical Uses of Atomic Radiation, pp. 471-589. Radioisotopes and Radiation, John H. Lawrence, Bernard Manowitz, and Benjamin S. Loeb, McGraw-Hill Book Company, New York 10036, 1964, 131 pp., $18.00. Chapter 1, Medical Diagnosis and Research, pp. 5-45, Chapter 2, Medical Therapy, pp. 49-62.

Popular Books Atoms Today and Tomorrow (revised edition), Margaret O. Hyde, McGraw-Hill Book Company, Inc., New York 10036, 1966, 160 pp., $3.25. Chapter 9, The Doctor and the Atom, pp 79101. Atomic Energy m Medicine, K. E. Hainan, Philosophical Library, Inc., New York 10016, 1958, 157 pp., $6.00. (Out of print but available through libraries.) Teach YourselJ Atomic Physics, James M. Valentine, The Macmillan Company, New York 10011, 1961, 192 pp., $1.95. (Out of print but available through libraries.) Chapter X, Medical and Biological Uses of Radioactive Isotopes, pp, 173-184. Atoms for Peace, Dj.vid O. Woodbury, Dodd, Mead & Company, New York 10016, 1965, 259 pp., $4 50 Pp. 174-191. The Atom at Work, Jacob Sacks, The Ronald P r e s s Company, New York 10010, 1956, 341 pp., $5.50. Chapter 13, Radioactive Isotopes in Hospital and Clinic, pp. 244-264.

Articles Ionizing Radiation and Medicine, S. Warren, Scientific American, 201- 164 (September 1959). Nuclear Nurses Learn to Tame the Atom, W. McGaffin, Today's Health, 37. 62 (December 1959). How Isotopes Aid Medicine in Tracking Down Your Ailments, J. Foster, Today's Health, 42. 40 (May 1964). Nuclear Energy as a Medical Tool, G. W. T r e s s e l , Today's Health, 43: 50 (May 1965).

47


Reports

Radioisotopes in Medicine

Radioisotopes m Medicine (SRlA-13), Stanford Research Institute, Clearinghouse for Federal Scientific and Technical Information, 5285 Port Royal Road, Springfield, Virginia 22151, 1959,180 pp., $3.00.

By E A R L W. P H E L A N

The following r e p o r t s a r e available from the Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402. Isotopes and Radiation Technology (Fall 1963), P. S. Baker, A. F . Rupp, and Associates, Oak Ridge National Laboratory, U. S. Atomic Energy Commission, 123 pp., $0 70. Radioisotopes m Medicine (ORO-125), Gould A. Andrews, Marshall Brucer, and Elizabeth B. Anderson, 1956, 817 pp., $6.00. Applications of Radioisotopes and Radiation m the Life Sciences, Hearings before the Subcommittee on Research, Development, and Radiation of the Joint Committee on Atomic Energy, 87th Congress, 1st Session, 1961, 513 pp., $1 50, Summary Analysis of the Hearings, 23 pp., $0.15.

INTRODUCTION

Motion Pictures

History

Available for loan without charge from the AEC Headquarters Film Library, Division of Public Information, U. S. Atomic Energy Commission, Washington, D. C. 20545 and from other AEC film libraries. Radioisotope Applications in Medicine, 26 minutes, black and white, sound, 1964. Produced by the Educational Broadcasting Corporation under the joint direction of the U. S. Atomic Energy Commission's Divisions of Isotopes Development and Nuclear Education and Training, and the Oak Ridge Institute of Nuclear Studies. This film traces the development of the use of radioisotopes and radiation in the field of medicine from the early work of Hevesy to the present. Descriptions of the following a r e given: study of cholesterol and a r t e r i o s c l e r o s i s , cobalt labeled vitamin Bi2 used to study pernicious anemia, history of iodine radioisotopes and the thyroid, brain tumor localization, determination of body fluid volumes, red cell lifetime, and use of radioisotopes for the treatment of various diseases. Medicine, 20 minutes, sound, color, 1957. Produced by the U. S. Information Agency. Four illustrations of the use of radioactive materials in diagnosis and therapy a r e given exact preoperative location of brain tumor, scanning and charting of thyroids, cancer therapy research, and the study of blood diseases and hardening of the a r t e r i e s . Radiation Protection m Nuclear Medicine, 45 m i n u t e s , sound, color, 1962. Produced by the Fordel Films for the Bureau of Medicine and Surgery of the U. S. Navy. This semitechnical film demonstrates the procedures devised for naval hospitals to protect against the gamma radiation emitted from materials used in radiation therapy.

48

The history of the u s e of radioisotopes for medical purposes i s filled with names of Nobel P r i z e w i n n e r s . It IS inspiring to read how g r e a t minds attacked puzzling phenomena, worked out the theoretical and p r a c t i c a l i m plications of what they observed, and w e r e rewarded by the highest honor in science. For example, in 1895 a G e r man physicist, Wilhelm Konrad Roentgen, n o t i c e d that c e r t a i n c r y s t a l s became luminescent when they were in the vicinity of a highly evacuated e l e c t r i c - d i s charge tube. Objects placed b e tween the tube and the c r y s t a l s s c r e e n e d out some of the invisible radiation that caused this effect, and he observed that the g r e a t e r the d e n s i t y of the object so placed, the g r e a t e r the s c r e e n Wilhelm Roentgen ing effect. He called this new radiation X r a y s , because x was the standard algebraic symbol for an unknown quantity. His discovery won him the first Nobel P r i z e in physics m 1901.

1


^ISitJ-

THE COVER This multi-detector positron scanner is used to locate t u m o r s . A radioisotopelabeled substance is injected into the body and subsequently concentrates in the tumor tissue. The radioisotope emits positrons that immediately decay and produce two gamma rays that travel in opposite directions. These rays a r e detected simultaneously on a pair of opposing detection crystals and a line is established along which the tumor is located. This method is one of many ways doctors use radioisotopes to combat disease. In this, as in many other procedures described in this booklet, the patient remains comfortable at all times.

The following films in the Magic of the Atom Series were produced by the Handel Film Corporation. They a r e each 12V'2 minutes long, have sound, and a r e in black and white. The Atom and the Doctor (1954) shows three applications of radioisotopes in medicine: testing for leukemia and other blood d i s orders with radioiron; diagnosis of thyroid conditions with radioiodine; and cancer r e s e a r c h and therapy with radiogallium. The Atom in the Hospital (1961) (available in color and black and white) illustrates the following facilities at the City of Hope Medical Center in Los Angeles: the stationary cobalt source that is used to treat various forms of malignancies; a rotational therapy unit called the " c e s i u m ring", which revolves around the patient and focuses its beam on the diseased area; and the total-body irradiation chamber for studying the effects of radiation on living things. Research with these facilities is explained. Atomic Biology for Medicine (1956) explains experiments p e r formed to discover effects of radiation on mammals. Atoms for Health (1956) outlines two methods of diagnosis and treatment possible with radiation: a diagnostic test of the liver, and cancer therapy with a radioactive cobalt device. Case histories a r e presented step-by-step. Radiation: Silent Servant of Mankind (1956) depicts four uses of controlled radiation that can benefit mankind: bombardment of plants from a radioactive cobalt source to induce genetic changes for study and crop improvement; irradiation of deep-seated tumors with a beam from a particle accelerator; therapy of thyroid cancer with radioactive iodine; and possibilities for treating brain tumors.

THE AUTHOR Earl W. Phelan is Professor of Chemistry at Tusculum College, Greeneville, Tennessee. From 1952 to 1965, he served as Staff A s s i s tant in the Laboratory Director's Office at Argonne National Laboratory, where his duties included editing the Argonne Reviews and supplying information to students. For 22 years prior to moving to Argonne he served as Head of the Chemistry Department of the Valdosta State College in Georgia. He received his B.S. and P h . D . d e g r e e s from Cornell University.

49


Radioisotopes in Medicine CONTENTS

PHOTO CREDITS Cover Courtesy Brookhaven National Laboiatory

General ElcLtnc Company Df^cot e) I ol thi L!i»n>iis Mary Elvira Weeks, Journal of Chemical Education Nobel Institute Chicago Wesley Memorial Hospital ( m a m photo) Lawrence Radiation Laboratory (LRL) Brookhaven National Laboratory' LRL LRL Los Alamos Scientific Laboratory LRL Argonne National Laboratory Paul V. Harper, M. D University of Texas. M. D. Ander'iOii Hospital and Tumor Institute

50

1 1 5 5 6 7 9

INTRODUCTION History What Is Radiation ? What Is Radioactivity ? What Are Radioisotopes ? How Are Radioisotopes Used? What Do We Mean by Tracer Atoms?

n 11 14 15 18 18 23 24 25 26 27 28 30 30

DIAGNOSIS Pinpointing Disease Arsenic-74 Chromium-51 Cobalt-60 Iodine-131 Iron-59 Phosphorus-32 Sodium-24 Technetium-99"' Thulium-170 and Gamma Radiography Tritium Activation Analysis Summary

31 31 32 32 33 35 37 38 41

THERAPY A Successful Case General Principles lodine-131 and Iodine-132 Boron-10 Phosphorus-32 Gold-198 Beads, Needles, and Applicators Teletherapy

43

CONCLUSIONS

44

APPENDIX

47

SUGGESTED REFERENCES


UNITED STATES ATOMIC ENERGY COMMISSION Dr. Glenn T. Seaborg, James T. Ramey Dr. Gerald F. Tape Wilfrid E. Johnson

owe OF A stmis ON

UNDERSTANDING THE ATOM

Chairman

Nuclear energy i s playing a vital role in the life of every man, woman, and child in the United States today. In the y e a r s ahead it will affect increasingly all the peoples of the e a r t h . It is e s s e n t i a l that all Americans gain an understanding of this vital force if they a r e to discharge thoughtfully t h e i r responsibilities a s citizens and if they a r e to r e a l i z e fully the myriad benefits that nuclear energy offers them. The United States Atomic Energy Commission provides this booklet to help you achieve such understanding.

^Edward J. Brunenkant Director Division of Technical Information

This booklet is one of the "Understanding the Atom'' Series. Comments a r e invited on this booklet and others in the s e r i e s ; please send them to the Division of Technical Information, U. S. Atomic Energy Commission, Washington, D. C. 20545. Published as part of the AEC's educational assistance program, the s e r i e s includes these titles: Accelerators Animals in Atomic Research Atomic Fuel Atomic Power Safety Atoms at the Science Fair Atoms in Agriculture Atoms, Nature, ami Man Careers in Atomic Energy Computers Controlled Nuclear Fusion Cryogenics, The Uncommon Cold Direct Conversion of Energy Fallout From Nuclear Tests Food Preservation by Irradiation Genetic Effects of Radiation Microstructure oj Matter Neutron Activation Analysis Nondestructive Testing Nuclear Clocks Nuclear Energy for Desalting Nuclear Power and Merchant Skipping Nuclear Power Plants

Nuclear Propulsion for Space Nuclear Reactors Nuclear Terms, A BrieJ Glossary Our Atomic World Plowshare Plutonium Power from Radioisotopes Power Reactors in Small Packages Radioactive Wastes Radioisotopes and Life Processes Radioisotopes in Industry Radioisotopes in Medicine Rare Earths Research Reactors SNAP, Nuclear Space Reactors Sources ot Nuclear Fuel Synthetic Transuranium Elements The Atom and the Ocean The Chemistry of the Noble Gases Whole Body Counters Your Body and Radiation

A single copy of any one booklet, or of no more than thiec different booklets, may be obtained free by writing to: USAEC, P. 0. BOX 62, OAK RIDGE, TENNESSEE

37830

Complete sets of the s e r i e s a r e available to school and public librarians, and to teachers who can make them available for reference or for use by groups. Requests should be made on school or library letterheads and indicate the proposed u s e . Students and teachers who need other material on specific aspects of nuclear science, or references to other reading material, may also write to the Oak Ridge a d d r e s s . Requests should state the topic of interest exactly, and the u s e intended. In all requests, include " Z i p Code" in return a d d r e s s .

Printed in the United States of America USAEC Division of Technical Information Extension, Oak Ridge, Tennessee August 1967


Radioisotopes in Medicine

U.S. ATOMIC ENERGY COMMISSION/Division of Technical Information

Radioisotopes in medicine (Atomic Energy Commission) USofA  
Radioisotopes in medicine (Atomic Energy Commission) USofA